P53

{{Short description|Mammalian protein found in humans}} {{other uses}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Lowercase title}} {{Infobox gene}} '''p53''', also known as '''tumor protein p53''', '''TP53''', '''cellular tumor antigen p53''' ([[UniProt]] name), or '''transformation-related protein 53 (TRP53)''' is a [[Regulation of gene expression|regulatory]] [[transcription factor]] protein that is often [[Mutation|mutated]] in human [[cancers]]. The p53 proteins (originally thought to be, and often spoken of as, a single protein) are crucial in [[vertebrate]]s, where they prevent cancer formation.<ref name="Surget">{{cite journal |vauthors=Surget S, Khoury MP, Bourdon JC |date=December 2013 |title=Uncovering the role of p53 splice variants in human malignancy: a clinical perspective |journal=OncoTargets and Therapy |volume=7 |pages=57–68 |doi=10.2147/OTT.S53876 |pmc=3872270 |pmid=24379683 |doi-access=free}}</ref> As such, p53 has been described as "the guardian of the [[genome]]" because of its role in conserving stability by preventing [[genome mutation]].<ref>{{cite journal |vauthors=Toufektchan E, Toledo F |date=May 2018 |title=The Guardian of the Genome Revisited: p53 Downregulates Genes Required for Telomere Maintenance, DNA Repair, and Centromere Structure |journal=Cancers |volume=10 |issue=5 |page=135 |doi=10.3390/cancers10050135 |pmc=5977108 |pmid=29734785 |doi-access=free}}</ref> Hence ''TP53''<ref group="note">[[Gene nomenclature#Vertebrate gene and protein symbol conventions|''italics'']] are used to denote the ''TP53'' gene name and distinguish it from the protein it encodes</ref> is classified as a [[tumor suppressor gene]].<ref name="pmid6396087">{{cite journal |vauthors=Matlashewski G, Lamb P, Pim D, Peacock J, Crawford L, Benchimol S |date=December 1984 |title=Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene |journal=The EMBO Journal |volume=3 |issue=13 |pages=3257–62 |doi=10.1002/j.1460-2075.1984.tb02287.x |pmc=557846 |pmid=6396087}}</ref><ref name="pmid3456488">{{cite journal |vauthors=Isobe M, Emanuel BS, Givol D, Oren M, Croce CM |year=1986 |title=Localization of gene for human p53 tumour antigen to band 17p13 |journal=Nature |volume=320 |issue=6057 |pages=84–5 |bibcode=1986Natur.320...84I |doi=10.1038/320084a0 |pmid=3456488 |s2cid=4310476}}</ref><ref name="pmid2047879">{{cite journal |vauthors=Kern SE, Kinzler KW, Bruskin A, Jarosz D, Friedman P, Prives C, Vogelstein B |date=June 1991 |title=Identification of p53 as a sequence-specific DNA-binding protein |journal=Science |volume=252 |issue=5013 |pages=1708–11 |bibcode=1991Sci...252.1708K |doi=10.1126/science.2047879 |pmid=2047879 |s2cid=19647885}}</ref><ref name="pmid 3001719">{{cite journal |vauthors=McBride OW, Merry D, Givol D |date=January 1986 |title=The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13) |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=83 |issue=1 |pages=130–4 |bibcode=1986PNAS...83..130M |doi=10.1073/pnas.83.1.130 |pmc=322805 |pmid=3001719 |doi-access=free}}</ref><ref name="Bourdon" />

The ''TP53'' gene is the most frequently mutated gene (>50%) in human cancer, indicating that the ''TP53'' gene plays a crucial role in preventing cancer formation.<ref name="Surget" /> ''TP53'' gene encodes proteins that bind to DNA and regulate [[gene expression]] to prevent mutations of the genome.<ref>{{cite book |title=The p53 family |date=2010 |publisher=Cold Spring Harbor Laboratory Press |isbn=978-0-87969-830-0 |veditors=Levine AJ, Lane DP |series=Cold Spring Harbor Perspectives in Biology |location=Cold Spring Harbor, N.Y.}}</ref> In addition to the full-length protein, the human ''TP53'' gene encodes at least 12 protein [[Protein isoform|isoforms]].<ref>{{cite journal |vauthors=Khoury MP, Bourdon JC |date=April 2011 |title=p53 Isoforms: An Intracellular Microprocessor? |journal=Genes Cancer |volume=2 |issue=4 |pages=453–65 |doi=10.1177/1947601911408893 |pmc=3135639 |pmid=21779513}}</ref>

Comparative genomic studies found pathogenic mutations absent in some Neanderthal populations, while modern humans exhibit an expansion of over 1,000 mutated variations.<ref name="Li2025">{{cite journal |vauthors=Li J, Zhao B, et al. |date=November 2025 |title=Pathogenic variation in human DNA damage repair genes was originated from the evolutionary process of modern humans |journal=Genes & Diseases |doi=10.1016/j.gendis.2025.101916 |article-number=101916|pmc=12859193 }}</ref> Evidence suggests that the vast majority of these protein-coding variants arose very recently in human history, specifically concentrated within a window of 5,000 to 10,000 years ago.<ref name="Fu2013">{{cite journal |vauthors=Fu W, O'Connor TD, et al. |date=January 2013 |title=Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants |url=http://nrs.harvard.edu/urn-3:HUL.InstRepos:11717639 |journal=Nature |volume=493 |issue=7431 |pages=216–220 |bibcode=2013Natur.493..216F |doi=10.1038/nature11690 |pmid=23201682 |pmc=3676746 }}</ref><ref name="Zhao2024">{{cite journal |vauthors=Zhao B, Li J, et al. |date=April 2024 |title=Pathogenic variants in human DNA damage repair genes mostly arose in recent human history |journal=BMC Cancer |volume=24 |issue=1 |doi=10.1186/s12885-024-12160-6 |pmc=10993466 |pmid=38575974 |doi-access=free |article-number=415}}</ref>

== Gene == In humans, the ''TP53'' gene is located on the short arm of [[chromosome 17 (human)|chromosome 17]] (17p13.1).<ref name="pmid6396087" /><ref name="pmid3456488" /><ref name="pmid2047879" /><ref name="pmid 3001719" /> The gene spans 20 [[Kilo-base pair|kb]], with a non-coding [[exon]] 1 and a very long first [[intron]] of 10 kb, overlapping the [[Hp53int1]] gene. The coding sequence contains five regions showing a high degree of conservation in vertebrates, predominantly in exons 2, 5, 6, 7 and 8, but the sequences found in invertebrates show only distant resemblance to mammalian TP53.<ref name="pmid10618702">{{cite journal |vauthors=May P, May E |date=December 1999 |title=Twenty years of p53 research: structural and functional aspects of the p53 protein |journal=Oncogene |volume=18 |issue=53 |pages=7621–36 |doi=10.1038/sj.onc.1203285 |pmid=10618702 |doi-access=free}}</ref> ''TP53'' [[orthologs]]<ref name="OrthoMaM">{{cite web |title=OrthoMaM phylogenetic marker: TP53 coding sequence |url=http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000141510_TP53.xml |archive-url=https://web.archive.org/web/20180317110251/http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000141510_TP53.xml |archive-date=2018-03-17 |access-date=2009-12-02}}</ref> have been identified in most [[mammals]] for which complete genome data are available. Elephants, with 20 genes for TP53, rarely get cancer.<ref>{{cite journal |vauthors=Sulak M, Fong L, Mika K, Chigurupati S, Yon L, Mongan NP, Emes RD, Lynch VJ |date=September 2016 |title=''TP53'' copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants |journal=eLife |volume=5 |bibcode=2016eLife...511994S |doi=10.7554/eLife.11994 |pmc=5061548 |pmid=27642012 |doi-access=free |article-number=e11994}}</ref>

== Structure == [[File:P53 Schematic.tif|thumb|right|A schematic of the known protein domains in p53 (NLS = Nuclear Localization Signal)|360x360px]] [[File:3KMD p53 DNABindingDomian.png|thumb|Crystal structure of four p53 DNA-binding domains (as found in the bioactive homo-tetramer)]]

The full-length p53 protein (p53α) comprises seven distinct [[protein domain]]s: # An acidic [[N-terminus]] [[transactivation domain]] (TAD), including activation domains 1 and 2 (AD1: residues 1–42; AD2: residues 43–63), which regulate transcription of several pro-apoptotic genes.<ref name="pmid9707426">{{cite journal |vauthors=Venot C, Maratrat M, Dureuil C, Conseiller E, Bracco L, Debussche L |date=August 1998 |title=The requirement for the p53 proline-rich functional domain for mediation of apoptosis is correlated with specific PIG3 gene transactivation and with transcriptional repression |journal=The EMBO Journal |volume=17 |issue=16 |pages=4668–79 |doi=10.1093/emboj/17.16.4668 |pmc=1170796 |pmid=9707426}}</ref> # A [[proline]]-rich domain (residues 64–92), involved in apoptotic function and nuclear export via [[MAPK]] signaling. # A central [[DNA-binding domain]] (DBD; residues 102–292), containing a zinc atom and multiple [[arginine]] residues, essential for sequence-specific DNA interaction and co-repressor binding such as [[LMO3]].<ref name="Larsen S, Yokochi T, Isogai E, Nakamura Y, Ozaki T, Nakagawara A 2010 252–7">{{cite journal |vauthors=Larsen S, Yokochi T, Isogai E, Nakamura Y, Ozaki T, Nakagawara A |date=February 2010 |title=LMO3 interacts with p53 and inhibits its transcriptional activity |journal=Biochemical and Biophysical Research Communications |volume=392 |issue=3 |pages=252–7 |bibcode=2010BBRC..392..252L |doi=10.1016/j.bbrc.2009.12.010 |pmid=19995558}}</ref> # A [[nuclear localization sequence]] (NLS; residues 316–325), required for nuclear import. # A homo-oligomerization domain (OD; residues 307–355), which mediates tetramerization—essential for p53 activity ''in vivo''. # A [[C-terminal]] regulatory domain (residues 356–393), which modulates the DNA-binding activity of the central domain.<ref name="pmid15713654">{{cite journal |vauthors=Harms KL, Chen X |date=March 2005 |title=The C terminus of p53 family proteins is a cell fate determinant |journal=Molecular and Cellular Biology |volume=25 |issue=5 |pages=2014–30 |doi=10.1128/MCB.25.5.2014-2030.2005 |pmc=549381 |pmid=15713654}}</ref>

Most cancer-associated mutations in ''TP53'' occur in the DBD, impairing DNA binding and transcriptional activation. These are typically [[recessive allele|recessive loss-of-function]] mutations. By contrast, mutations in the OD can exert [[dominant negative]] effects by forming inactive complexes with [[wild-type]] p53.

Wild-type p53 is a [[labile]] protein containing both folded and [[intrinsically unstructured proteins|intrinsically disordered]] regions that act synergistically.<ref name="pmid12367518">{{cite journal |vauthors=Bell S, Klein C, Müller L, Hansen S, Buchner J |date=October 2002 |title=p53 contains large unstructured regions in its native state |journal=Journal of Molecular Biology |volume=322 |issue=5 |pages=917–27 |doi=10.1016/S0022-2836(02)00848-3 |pmid=12367518}}</ref>

Although designated as a 53&nbsp;kDa protein by [[SDS-PAGE]], the actual molecular weight of p53α is 43.7&nbsp;kDa. The discrepancy is due to its high [[proline]] content, which slows electrophoretic migration.<ref name="pmid7107651">{{cite journal |vauthors=Ziemer MA, Mason A, Carlson DM |date=September 1982 |title=Cell-free translations of proline-rich protein mRNAs |journal=The Journal of Biological Chemistry |volume=257 |issue=18 |pages=11176–80 |doi=10.1016/S0021-9258(18)33948-6 |pmid=7107651 |doi-access=free}}</ref>

== Tetramerization == p53 initially forms [[protein dimer|dimers]] cotranslationally during protein synthesis on ribosomes.<ref name="Nicholls_2002">{{cite journal |vauthors=Nicholls CD, McLure KG, Shields MA, Lee PW |date=April 2002 |title=Biogenesis of p53 involves cotranslational dimerization of monomers and posttranslational dimerization of dimers. Implications on the dominant negative effect |journal=The Journal of Biological Chemistry |volume=277 |issue=15 |pages=12937–12945 |doi=10.1074/jbc.M108815200 |pmid=11805092 |doi-access=free}}</ref> Each dimer consists of two p53 monomers joined through their oligomerization domains.<ref name="Suri_1999">{{cite journal |vauthors=Suri V, Lanjuin A, Rosbash M |date=February 1999 |title=TIMELESS-dependent positive and negative autoregulation in the Drosophila circadian clock |journal=The EMBO Journal |volume=18 |issue=3 |pages=675–686 |doi=10.1093/emboj/18.3.675 |pmc=1171160 |pmid=9927427}}</ref>

The dimerization interface spans residues 325–356 and includes a [[beta-strand]] (residues 325–333), a [[alpha-helix]] (residues 335–356), and a sharp turn at the conserved hinge residue Gly334. This configuration links the beta-strand and alpha-helix to form a V-shaped monomer topology. The beta-strand contributes to the formation of an antiparallel intermolecular [[beta-sheet]] between two p53 monomers, stabilized by [[hydrophobic]] interactions involving Phe328, Leu330, and Ile332. The alpha-helix forms an antiparallel [[coiled-coil]] between the two monomers, with a packing angle of 156°. Helix–helix interactions are stabilized by hydrophobic contacts (e.g., Phe338, Phe341, Leu344) and electrostatic interactions, such as the Arg337–Asp352 [[salt bridge]].

Following dimer formation, p53 dimers associate posttranslationally to form [[tetramer]]s (dimers of dimers).<ref name="Nicholls_2002" /><ref name="Natan_2009">{{cite journal |vauthors=Natan E, Hirschberg D, Morgner N, Robinson CV, Fersht AR |date=August 2009 |title=Ultraslow oligomerization equilibria of p53 and its implications |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=106 |issue=34 |pages=14327–14332 |bibcode=2009PNAS..10614327N |doi=10.1073/pnas.0907840106 |pmc=2731847 |pmid=19667193 |doi-access=free}}</ref> The tetramerization domain (residues 325–356) plays a central role in stabilizing the tetrameric structure.<ref name="Natan_2009" /> In the tetramer, the two primary dimers associate at an angle described as "roughly orthogonal," with a helix bundle packing angle (θ) of approximately 80°.

Tetramers represent the active form of p53 for DNA binding and transcriptional regulation.<ref name="Ho_2006">{{cite journal |vauthors=Ho WC, Fitzgerald MX, Marmorstein R |date=July 2006 |title=Structure of the p53 core domain dimer bound to DNA |journal=The Journal of Biological Chemistry |volume=281 |issue=29 |pages=20494–20502 |doi=10.1074/jbc.M603634200 |pmid=16717092 |doi-access=free}}</ref><ref name="Suri_1999" />

== Isoforms ==

Like 95% of human genes, ''TP53'' encodes multiple proteins, collectively known as the '''p53 isoforms'''.<ref name="Surget" /> These vary in size from 3.5 to 43.7&nbsp;kDa. Since their initial discovery in 2005, 12 human p53 isoforms have been identified: p53α, p53β, p53γ, ∆40p53α, ∆40p53β, ∆40p53γ, ∆133p53α, ∆133p53β, ∆133p53γ, ∆160p53α, ∆160p53β, and ∆160p53γ. Isoform expression is tissue-dependent, and p53α is never expressed alone.<ref name="Bourdon">{{cite journal |vauthors=Bourdon JC, Fernandes K, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP, Saville MK, Lane DP |date=September 2005 |title=p53 isoforms can regulate p53 transcriptional activity |journal=Genes & Development |volume=19 |issue=18 |pages=2122–37 |doi=10.1101/gad.1339905 |pmc=1221884 |pmid=16131611}}</ref>

The isoforms differ by the inclusion or exclusion of specific domains. Some, such as Δ133p53β/γ and Δ160p53α/β/γ, lack the transactivation or proline-rich domains and are deficient in apoptosis induction, illustrating the functional diversity of ''TP53''.<ref>{{cite journal |vauthors=Zhu J, Zhang S, Jiang J, Chen X |date=December 2000 |title=Definition of the p53 functional domains necessary for inducing apoptosis |journal=The Journal of Biological Chemistry |volume=275 |issue=51 |pages=39927–34 |doi=10.1074/jbc.M005676200 |pmid=10982799 |doi-access=free}}</ref><ref name="pmid21779513" />

Isoforms are generated through multiple mechanisms: * Alternative splicing of intron 9 creates the β and γ isoforms with altered C-termini. * An internal promoter in intron 4 produces the ∆133 and ∆160 isoforms, which lack part of the TAD and DBD. * Alternative translation initiation at codons 40 or 160 results in ∆40p53 and ∆160p53 isoforms, respectively.<ref name="Bourdon" />

== Function ==

=== DNA damage and repair === [[File:Activation of p53 in response to stress signals initiates its transcriptional activity, leading to the activation of cellular protective pathways.jpg|thumb|Activation of p53 in response to stress signals initiates its transcriptional activity, leading to the activation of cellular protective pathways<ref name="Janic_2025"/>]]

p53 regulates cell cycle progression, [[apoptosis]], and [[Genome instability|genomic stability]] through multiple mechanisms:

* Activates [[DNA repair]] proteins in response to DNA damage,<ref name="Janic_2025">{{cite journal |vauthors=Janic A, Abad E, Amelio I |date=January 2025 |title=Decoding p53 tumor suppression: a crosstalk between genomic stability and epigenetic control? |journal=Cell Death and Differentiation |volume=32 |issue=1 |pages=1–8 |doi=10.1038/s41418-024-01259-9 |pmc=11742645 |pmid=38379088 |doi-access=free}}{{Creative Commons text attribution notice|cc=by4|from this source=yes}}</ref> suggesting a potential role in [[aging]].<ref>{{cite book |title=Developmental Biology, 10th ed. |vauthors=Gilbert SF |publisher=Sinauer Associates, Inc. Publishers |location=Sunderland, MA USA |page=588}}</ref> * Arrests the cell cycle at the [[G1/S transition|G1/S checkpoint]] upon DNA damage, allowing time for repair before progression. * Initiates apoptosis if the damage is beyond repair. * Essential for the [[Cellular senescence|senescence]] response triggered by short [[telomere]]s.

p53 functions as a transcription factor by binding DNA as a tetramer, a structure that is essential for its stability and effective DNA binding activity.<ref name="Engeland_2022" /> Once bound to DNA, p53 induces the transcription of numerous genes involved in DNA repair pathways. This includes components of [[base excision repair]] (BER) such as OGG1 and MUTYH, [[nucleotide excision repair]] (NER) factors like DDB2 and XPC, [[mismatch repair]] (MMR) genes such as MSH2 and MLH1, and elements of [[homologous recombination]] (HR) and [[non-homologous end-joining]] (NHEJ) repair.<ref name="Williams_2016">{{cite journal |vauthors=Williams AB, Schumacher B |date=May 2016 |title=p53 in the DNA-Damage-Repair Process |journal=Cold Spring Harbor Perspectives in Medicine |volume=6 |issue=5 |doi=10.1101/cshperspect.a026070 |pmc=4852800 |pmid=27048304 |article-number=a026070}}</ref><ref name="Adimoolam_2003">{{cite journal |vauthors=Adimoolam S, Ford JM |date=September 2003 |title=p53 and regulation of DNA damage recognition during nucleotide excision repair |journal=DNA Repair |volume=2 |issue=9 |pages=947–54 |doi=10.1016/s1568-7864(03)00087-9 |pmid=12967652}}</ref> These transcriptional responses are crucial for the [[DNA damage response]] (DDR), allowing cells to efficiently repair damaged DNA and maintain genomic integrity. While p53's role is most clearly defined in transcriptional activation of repair genes, it also participates in non-transcriptional regulation of DNA repair processes, particularly in HR and NHEJ, by modulating protein interactions and chromatin accessibility.<ref name="Williams_2016" /><ref name="Gatz_2006">{{cite journal |vauthors=Gatz SA, Wiesmüller L |date=June 2006 |title=p53 in recombination and repair |journal=Cell Death and Differentiation |volume=13 |issue=6 |pages=1003–16 |doi=10.1038/sj.cdd.4401903 |pmid=16543940}}</ref>

p53 binds specific elements in the promoter of target genes, including [[CDKN1A]], which encodes [[p21]].<ref name="Engeland_2022">{{cite journal |vauthors=Engeland K |date=May 2022 |title=Cell cycle regulation: p53-p21-RB signaling |journal=Cell Death and Differentiation |volume=29 |issue=5 |pages=946–960 |doi=10.1038/s41418-022-00988-z |pmc=9090780 |pmid=35361964}}</ref><ref name="Jung_2010">{{cite journal |vauthors=Jung YS, Qian Y, Chen X |date=July 2010 |title=Examination of the expanding pathways for the regulation of p21 expression and activity |journal=Cellular Signalling |volume=22 |issue=7 |pages=1003–12 |doi=10.1016/j.cellsig.2010.01.013 |pmc=2860671 |pmid=20100570}}</ref> Upon activation by p53, p21 inhibits [[cyclin-dependent kinase]]s, leading to [[Induced cell cycle arrest|cell cycle arrest]] and contributing to [[tumor suppression]].<ref name="Engeland_2022" /><ref name="Sullivan_2018">{{cite journal |vauthors=Sullivan KD, Galbraith MD, Andrysik Z, Espinosa JM |date=January 2018 |title=Mechanisms of transcriptional regulation by p53 |journal=Cell Death and Differentiation |volume=25 |issue=1 |pages=133–143 |doi=10.1038/cdd.2017.174 |pmc=5729533 |pmid=29125602}}</ref> However, p21 can also be induced independently of p53 during processes such as differentiation, development, and in response to serum stimulation.<ref name="Jung_2010" />

p21 (WAF1) binds to [[cyclin]]-[[Cyclin-dependent kinase|CDK]] complexes (notably [[CDK2]], [[CDK1]], [[CDK4]], and [[CDK6]]), inhibiting their activity and blocking the G1/S transition.<ref name="Al_Bitar_2019">{{cite journal |vauthors=Al Bitar S, Gali-Muhtasib H |date=September 2019 |title=The Role of the Cyclin Dependent Kinase Inhibitor p21cip1/waf1 in Targeting Cancer: Molecular Mechanisms and Novel Therapeutics |journal=Cancers |volume=11 |issue=10 |page=1475 |doi=10.3390/cancers11101475 |pmc=6826572 |pmid=31575057 |doi-access=free}}</ref><ref name="Karimian_2016">{{cite journal |vauthors=Karimian A, Ahmadi Y, Yousefi B |date=June 2016 |title=Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage |journal=DNA Repair |volume=42 |pages=63–71 |doi=10.1016/j.dnarep.2016.04.008 |pmid=27156098}}</ref> This inhibition enforces a cell cycle pause that allows DNA repair to occur. In cells with functional p53, p21 is upregulated in response to DNA damage, ensuring this checkpoint control. In contrast, p53 mutations impair p21 induction and compromise this control.<ref name="Engeland_2022" />

In [[human embryonic stem cell]]s (hESCs), although p21 mRNA is upregulated following DNA damage, the protein is not detectable. This reflects a nonfunctional p53-p21 axis at the G1/S checkpoint.<ref name="Ayaz_2022">{{cite journal |vauthors=Ayaz G, Yan H, Malik N, Huang J |date=October 2022 |title=An Updated View of the Roles of p53 in Embryonic Stem Cells |journal=Stem Cells |volume=40 |issue=10 |pages=883–891 |doi=10.1093/stmcls/sxac051 |pmc=9585900 |pmid=35904997}}</ref> This discrepancy is largely due to post-transcriptional repression, particularly by the miR-302 family of microRNAs, which inhibit p21 translation.<ref name="Dolezalova_2012">{{cite journal |vauthors=Dolezalova D, Mraz M, Barta T, Plevova K, Vinarsky V, Holubcova Z, Jaros J, Dvorak P, Pospisilova S, Hampl A |date=July 2012 |title=MicroRNAs regulate p21(Waf1/Cip1) protein expression and the DNA damage response in human embryonic stem cells |journal=Stem Cells |volume=30 |issue=7 |pages=1362–72 |doi=10.1002/stem.1108 |pmid=22511267}}</ref> Although p53 binds the CDKN1A promoter in hESCs, it does not regulate miR-302, which is constitutively expressed and suppresses p21 expression.<ref name="Dolezalova_2012" /><ref name="Ayaz_2022" />

The p53 pathway is interconnected with the [[Retinoblastoma protein|RB1]] pathway via p14^ARF, which links the regulation of these key tumor suppressors.<ref name="pmid9744267">{{cite journal |vauthors=Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL, Vousden KH |date=September 1998 |title=p14ARF links the tumour suppressors RB and p53 |journal=Nature |volume=395 |issue=6698 |pages=124–5 |bibcode=1998Natur.395..124B |doi=10.1038/25867 |pmid=9744267 |s2cid=4355786}}</ref>

p53 expression can be induced by [[UV radiation]], which also causes DNA damage. In this context, p53 activation can initiate processes that lead to [[sun tanning|melanin production and tanning]].<ref>{{cite magazine |date=March 17, 2007 |title=Genome's guardian gets a tan started |url=https://www.newscientist.com/channel/health/mg19325955.800-genomes-guardian-gets-a-tan-started.html |access-date=2007-03-29 |magazine=New Scientist}}</ref><ref name="pmid17350573">{{cite journal |vauthors=Cui R, Widlund HR, Feige E, Lin JY, Wilensky DL, Igras VE, D'Orazio J, Fung CY, Schanbacher CF, Granter SR, Fisher DE |date=March 2007 |title=Central role of p53 in the suntan response and pathologic hyperpigmentation |journal=Cell |volume=128 |issue=5 |pages=853–64 |bibcode=2007Cell..128..853C |doi=10.1016/j.cell.2006.12.045 |pmid=17350573 |doi-access=free}}</ref>

=== Stem cells === Levels of p53 play an important role in the maintenance of stem cells throughout development and the rest of human life.<ref>{{Cite journal |vauthors=Fu X, Wu S, Li B, Xu Y, Liu J |date=2020 |title=Functions of p53 in pluripotent stem cells |journal=Oxford Academic |volume=11 |issue=1 |pages=71–78 |doi=10.1007/s13238-019-00665-x |pmc=6949194 |pmid=31691903}}</ref>

In human [[embryonic stem cell]]s (hESCs)s, p53 is maintained at low inactive levels.<ref name="Jain AK p53">{{cite journal |vauthors=Jain AK, Allton K, Iacovino M, Mahen E, Milczarek RJ, Zwaka TP, Kyba M, Barton MC |year=2012 |title=p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells |journal=PLOS Biology |volume=10 |issue=2 |doi=10.1371/journal.pbio.1001268 |pmc=3289600 |pmid=22389628 |doi-access=free |article-number=e1001268}}</ref> This is because activation of p53 leads to rapid differentiation of hESCs.<ref>{{cite journal |vauthors=Maimets T, Neganova I, Armstrong L, Lako M |date=September 2008 |title=Activation of p53 by nutlin leads to rapid differentiation of human embryonic stem cells |journal=Oncogene |volume=27 |issue=40 |pages=5277–87 |doi=10.1038/onc.2008.166 |pmid=18521083 |doi-access=free}}</ref> Studies have shown that knocking out p53 delays differentiation and that adding p53 causes spontaneous differentiation, showing how p53 promotes differentiation of hESCs and plays a key role in cell cycle as a differentiation regulator. When p53 becomes stabilized and activated in hESCs, it increases p21 to establish a longer G1. This typically leads to abolition of S-phase entry, which stops the cell cycle in G1, leading to differentiation. Work in mouse embryonic stem cells has recently shown however that the expression of P53 does not necessarily lead to differentiation.<ref>{{cite journal |vauthors=ter Huurne M, Peng T, Yi G, van Mierlo G, Marks H, Stunnenberg HG |date=February 2020 |title=Critical role for P53 in regulating the cell cycle of ground state embryonic stem cells |journal=Stem Cell Reports |volume=14 |issue=2 |pages=175–183 |doi=10.1016/j.stemcr.2020.01.001 |pmc=7013234 |pmid=32004494 |doi-access=free}}</ref> p53 also activates [[MIR34A|miR-34a]] and [[Mir-145|miR-145]], which then repress the hESCs pluripotency factors, further instigating differentiation.<ref name="Jain AK p53" />

In adult stem cells, p53 regulation is important for maintenance of stemness in [[Stem-cell niche|adult stem cell niches]]. Mechanical signals such as [[hypoxia (medical)|hypoxia]] affect levels of p53 in these niche cells through the [[hypoxia inducible factors]], [[HIF1A|HIF-1α]] and [[HIF-2α]]. While HIF-1α stabilizes p53, HIF-2α suppresses it.<ref>{{cite journal |vauthors=Das B, Bayat-Mokhtari R, Tsui M, Lotfi S, Tsuchida R, Felsher DW, Yeger H |date=August 2012 |title=HIF-2α suppresses p53 to enhance the stemness and regenerative potential of human embryonic stem cells |journal=Stem Cells |volume=30 |issue=8 |pages=1685–95 |doi=10.1002/stem.1142 |pmc=3584519 |pmid=22689594}}</ref> Suppression of p53 plays important roles in cancer stem cell phenotype, induced pluripotent stem cells and other stem cell roles and behaviors, such as blastema formation. Cells with decreased levels of p53 have been shown to reprogram into stem cells with a much greater efficiency than normal cells.<ref>{{cite journal |vauthors=Lake BB, Fink J, Klemetsaune L, Fu X, Jeffers JR, Zambetti GP, Xu Y |date=May 2012 |title=Context-dependent enhancement of induced pluripotent stem cell reprogramming by silencing Puma |journal=Stem Cells |volume=30 |issue=5 |pages=888–97 |doi=10.1002/stem.1054 |pmc=3531606 |pmid=22311782}}</ref><ref>{{cite journal |vauthors=Marión RM, Strati K, Li H, Murga M, Blanco R, Ortega S, Fernandez-Capetillo O, Serrano M, Blasco MA |date=August 2009 |title=A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity |journal=Nature |volume=460 |issue=7259 |pages=1149–53 |bibcode=2009Natur.460.1149M |doi=10.1038/nature08287 |pmc=3624089 |pmid=19668189}}</ref> Papers suggest that the lack of cell cycle arrest and apoptosis gives more cells the chance to be reprogrammed. Decreased levels of p53 were also shown to be a crucial aspect of [[blastema]] formation in the legs of salamanders.<ref>{{cite journal |vauthors=Yun MH, Gates PB, Brockes JP |date=October 2013 |title=Regulation of p53 is critical for vertebrate limb regeneration |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=110 |issue=43 |pages=17392–7 |bibcode=2013PNAS..11017392Y |doi=10.1073/pnas.1310519110 |pmc=3808590 |pmid=24101460 |doi-access=free}}</ref> p53 regulation is very important in acting as a barrier between stem cells and a differentiated stem cell state, as well as a barrier between stem cells being functional and being cancerous.<ref>{{cite journal |vauthors=Aloni-Grinstein R, Shetzer Y, Kaufman T, Rotter V |date=August 2014 |title=p53: the barrier to cancer stem cell formation |journal=FEBS Letters |volume=588 |issue=16 |pages=2580–9 |bibcode=2014FEBSL.588.2580A |doi=10.1016/j.febslet.2014.02.011 |pmid=24560790 |s2cid=37901173 |doi-access=free}}</ref>

=== Other === [[File:P53 and angiogenesis.png|thumb|490x490px|An overview of the molecular mechanism of action of p53 on the angiogenesis<ref name="Babaei_2021">{{cite journal |vauthors=Babaei G, Aliarab A, Asghari Vostakolaei M, Hotelchi M, Neisari R, Gholizadeh-Ghaleh Aziz S, Bazl MR |date=November 2021 |title=Crosslink between p53 and metastasis: focus on epithelial-mesenchymal transition, cancer stem cell, angiogenesis, autophagy, and anoikis |journal=Molecular Biology Reports |volume=48 |issue=11 |pages=7545–7557 |doi=10.1007/s11033-021-06706-1 |pmid=34519942 |s2cid=237506513}}</ref>]] Apart from the cellular and molecular effects above, p53 has a tissue-level anticancer effect that works by inhibiting [[angiogenesis]].<ref name = "Babaei_2021" /> As tumors grow they need to recruit new blood vessels to supply them, and p53 inhibits that by (i) interfering with regulators of [[tumor hypoxia]] that also affect angiogenesis, such as HIF1 and HIF2, (ii) inhibiting the production of angiogenic promoting factors, and (iii) directly increasing the production of angiogenesis inhibitors, such as [[arresten]].<ref>{{cite journal |vauthors=Teodoro JG, Evans SK, Green MR |date=November 2007 |title=Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome |journal=Journal of Molecular Medicine |type=Review |volume=85 |issue=11 |pages=1175–1186 |doi=10.1007/s00109-007-0221-2 |pmid=17589818 |s2cid=10094554}}</ref><ref>{{cite journal |vauthors=Assadian S, El-Assaad W, Wang XQ, Gannon PO, Barrès V, Latour M, Mes-Masson AM, Saad F, Sado Y, Dostie J, Teodoro JG |date=March 2012 |title=p53 inhibits angiogenesis by inducing the production of Arresten |journal=Cancer Research |volume=72 |issue=5 |pages=1270–1279 |doi=10.1158/0008-5472.CAN-11-2348 |pmid=22253229 |doi-access=free}}</ref>

p53 by regulating [[leukemia inhibitory factor|Leukemia Inhibitory Factor]] has been shown to facilitate [[Implantation (human embryo)|implantation]] in the mouse and possibly human reproduction.<ref name="pmid18046411">{{cite journal |vauthors=Hu W, Feng Z, Teresky AK, Levine AJ |date=November 2007 |title=p53 regulates maternal reproduction through LIF |journal=Nature |volume=450 |issue=7170 |pages=721–4 |bibcode=2007Natur.450..721H |doi=10.1038/nature05993 |pmid=18046411 |s2cid=4357527}}</ref>

The immune response to infection also involves p53 and [[NF-κB]]. Checkpoint control of the [[cell cycle]] and of [[apoptosis]] by p53 is inhibited by some infections such as [[Mycoplasma]] bacteria,<ref>{{cite journal |vauthors=Borchsenius SN, Daks A, Fedorova O, Chernova O, Barlev NA |date=January 2018 |title=Effects of mycoplasma infection on the host organism response via p53/NF-κB signaling |journal=Journal of Cellular Physiology |volume=234 |issue=1 |pages=171–180 |doi=10.1002/jcp.26781 |pmid=30146800}}</ref> raising the specter of [[carcinogenesis|oncogenic infection]].

== Regulation == [[File:P53 pathways.jpg|300px|right|thumb|'''p53 pathway''': In a normal cell, p53 is inactivated by its negative regulator, mdm2. Upon DNA damage or other stress, the p53-mdm2 complex dissociates. Activated p53 can induce [[Induced cell cycle arrest|cell cycle arrest]] for repair or initiate apoptosis. The mechanism behind this decision is not fully understood.]]

=== Basal regulation === Under normal, unstressed conditions, p53 is maintained at low levels through continuous degradation mediated by the [[E3 ubiquitin ligase]] [[MDM2]] (HDM2 in humans).<ref name="Bykove2018">{{cite journal | vauthors = Bykov VJ, Eriksson SE, Bianchi J, Wiman KG | title = Targeting mutant p53 for efficient cancer therapy | journal = Nature Reviews. Cancer | volume = 18 | issue = 2 | pages = 89–102 | date = February 2018 | pmid = 29242642 | doi = 10.1038/nrc.2017.109 | s2cid = 4552678 }}</ref> MDM2 binds p53, exports it from the nucleus, and targets it for [[proteasome|proteasomal]] degradation. Notably, p53 transcriptionally activates ''MDM2'', establishing a classic [[negative feedback]] loop.

This feedback loop gives rise to damped oscillations in p53 levels, as demonstrated both experimentally<ref>{{cite journal |vauthors=Geva-Zatorsky N, Rosenfeld N, Itzkovitz S, Milo R, Sigal A, Dekel E, Yarnitzky T, Liron Y, Polak P, Lahav G, Alon U |date=June 2006 |title=Oscillations and variability in the p53 system |journal=Molecular Systems Biology |volume=2 |doi=10.1038/msb4100068 |pmc=1681500 |pmid=16773083 |article-number=2006.0033}}</ref> and in [[mathematical modelling|mathematical models]].<ref name="Explaining oscillations and variabi">{{cite journal |vauthors=Proctor CJ, Gray DA |date=August 2008 |title=Explaining oscillations and variability in the p53-Mdm2 system |journal=BMC Systems Biology |volume=2 |issue=75 |doi=10.1186/1752-0509-2-75 |pmc=2553322 |pmid=18706112 |doi-access=free |article-number=75}}</ref><ref>{{cite journal |vauthors=Chong KH, Samarasinghe S, Kulasiri D |date=December 2013 |title=Mathematical modelling of p53 basal dynamics and DNA damage response |journal=C-fACS |volume=259 |issue=20th International Congress on Mathematical Modelling and Simulation |pages=670–6 |doi=10.1016/j.mbs.2014.10.010 |pmid=25433195}}</ref> These oscillations may determine cell fate decisions between survival and apoptosis.<ref>{{cite journal |vauthors=Purvis JE, Karhohs KW, Mock C, Batchelor E, Loewer A, Lahav G |date=June 2012 |title=p53 dynamics control cell fate |journal=Science |volume=336 |issue=6087 |pages=1440–1444 |bibcode=2012Sci...336.1440P |doi=10.1126/science.1218351 |pmc=4162876 |pmid=22700930}}</ref>

=== Activation by cellular stress === p53 is activated in response to a range of cellular stressors, including [[DNA damage]] (for example from [[ultraviolet]] or [[ionizing radiation]]), [[osmotic shock]], ribonucleotide depletion, [[oncogene]] activation, and some viral infections.<ref name="Ljungman2000">{{cite journal | vauthors = Ljungman M | title = Dial 9-1-1 for p53: mechanisms of p53 activation by cellular stress | journal = Neoplasia | volume = 2 | issue = 3 | pages = 208–225 | date = 2000 | pmid = 10935507 | pmc = 1507568 | doi = 10.1038/sj.neo.7900080 }}</ref><ref name="AppellaAnderson2001">{{cite journal | vauthors = Appella E, Anderson CW | title = Post-translational modifications and activation of p53 by genotoxic stresses | journal = European Journal of Biochemistry | volume = 268 | issue = 10 | pages = 2764–2772 | date = May 2001 | pmid = 11358490 | doi = 10.1046/j.1432-1327.2001.02225.x | bibcode = 2001EJBio.268.2764A }}</ref>

Activation involves stabilization of the p53 protein, resulting in its accumulation in the nucleus, and regulatory changes that promote sequence-specific DNA binding and transcriptional activation of target genes.<ref name="AppellaAnderson2001"/><ref name="Lavin2006">{{cite journal | vauthors = Lavin MF, Gueven N | title = The complexity of p53 stabilization and activation | journal = Cell Death and Differentiation | volume = 13 | issue = 6 | pages = 941–950 | date = June 2006 | pmid = 16601750 | doi = 10.1038/sj.cdd.4401925 }}</ref> These processes are initiated in part by phosphorylation of residues in the N-terminal transactivation domain by stress-activated [[protein kinase|kinases]].<ref name="AppellaAnderson2001"/><ref name="Lavin2006"/> Phosphorylation of sites within the Mdm2-binding region (for example Ser20) can reduce binding to [[MDM2]] and thereby decrease ubiquitin-mediated degradation of p53.<ref name="Chehab1999">{{cite journal | vauthors = Chehab NH, Malikzay A, Stavridi ES, Halazonetis TD | title = Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 24 | pages = 13777–13782 | date = November 1999 | pmid = 10570149 | pmc = 24141 | doi = 10.1073/pnas.96.24.13777 | doi-access = free | bibcode = 1999PNAS...9613777C }}</ref><ref name="BrooksGu2006">{{cite journal | vauthors = Brooks CL, Gu W | title = p53 ubiquitination: Mdm2 and beyond | journal = Molecular Cell | volume = 21 | issue = 3 | pages = 307–315 | date = February 2006 | pmid = 16455486 | pmc = 3737769 | doi = 10.1016/j.molcel.2006.01.020 }}</ref>

=== Stress-responsive kinases === Kinases that regulate p53 phosphorylation can be divided into two broad groups. One group includes members of the [[mitogen-activated protein kinase|MAPK]] pathways, including JNK1–3, ERK1/2 and p38 MAPK, which are activated by diverse cellular stresses such as oxidative stress and heat shock.<ref>{{cite journal | vauthors = Cargnello M, Roux PP | title = Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases | journal = Microbiology and Molecular Biology Reviews | volume = 75 | issue = 1 | pages = 50–83 | date = March 2011 | pmid = 21372320 | pmc = 3063353 | doi = 10.1128/MMBR.00031-10 }}</ref> A second group comprises [[DNA damage response]] kinases, including [[ATM]], [[Ataxia telangiectasia and Rad3 related|ATR]] and [[DNA-PKcs|DNA-PK]], together with downstream checkpoint kinases such as [[CHK1]] and [[CHK2]], which are activated by DNA damage and replication stress and contribute to p53 regulation through phosphorylation-dependent signalling.<ref>{{cite journal | vauthors = Blackford AN, Jackson SP | title = ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response | journal = Molecular Cell | volume = 66 | issue = 6 | pages = 801–817 | date = June 2017 | pmid = 28622525 | doi = 10.1016/j.molcel.2017.05.015 }}</ref><ref>{{cite journal | vauthors = Ou YH, Chung PH, Sun TP, Shieh SY | title = p53 C-terminal phosphorylation by CHK1 and CHK2 participates in the regulation of DNA-damage-induced C-terminal acetylation | journal = Molecular Biology of the Cell | volume = 16 | issue = 4 | pages = 1684–1695 | date = April 2005 | pmid = 15659650 | pmc = 1073652 | doi = 10.1016/j.molcel.2004.12.023 }}</ref>

Additional kinases implicated in p53 phosphorylation include the [[CDK-activating kinase]] (CAK; CDK7–cyclin H–MAT1), which has been shown to phosphorylate p53 (for example at Ser33) in vitro and in vivo,<ref>{{cite journal | vauthors = Ko LJ, Shieh SY, Chen X, Jayaraman L, Tamai K, Taya Y, Prives C, Pan ZQ | display-authors = 6 | title = p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner | journal = Molecular and Cellular Biology | volume = 17 | issue = 12 | pages = 7220–7229 | date = December 1997 | pmid = 9372954 | pmc = 232579 | doi = 10.1128/MCB.17.12.7220 | doi-access = free }}</ref> and [[TP53RK]] (PRPK), which has been reported to phosphorylate p53 at Ser15.<ref>{{cite web |title=TP53RK (TP53-regulating kinase) (Homo sapiens) |website=[[UniProt]] |url=https://www.uniprot.org/uniprotkb/Q96S44/entry |access-date=19 January 2026}}</ref>

Oncogene-induced activation of p53 can also occur via [[p14ARF]] (ARF), which inhibits the p53 antagonist [[MDM2]] and thereby stabilizes p53.<ref>{{cite journal | vauthors = Van Maerken T, Vandesompele J, Rihani A, De Paepe A, Speleman F | title = Escape from p53-mediated tumor surveillance in neuroblastoma: switching off the p14(ARF)-MDM2-p53 axis | journal = Cell Death and Differentiation | volume = 16 | issue = 12 | pages = 1563–1572 | date = December 2009 | pmid = 19779493 | doi = 10.1038/cdd.2009.138 }}</ref><ref>{{cite journal | vauthors = Llanos S, Clark PA, Rowe J, Peters G | title = Stabilization of p53 by p14ARF without relocation of MDM2 to the nucleolus | journal = Nature Cell Biology | volume = 3 | issue = 5 | pages = 445–452 | date = May 2001 | pmid = 11331871 | doi = 10.1038/35074506 }}</ref>

=== Deubiquitination === Several [[deubiquitinating enzyme]]s (DUBs) modulate p53 stability by removing ubiquitin chains. [[USP7]], also known as HAUSP, can deubiquitinate both p53 and MDM2. In unstressed cells, HAUSP preferentially stabilizes MDM2, and its depletion may paradoxically increase p53 levels. [[USP42]] is another DUB that stabilizes p53 and enhances its ability to respond to stress.<ref>{{cite journal |vauthors=Hock AK, Vigneron AM, Carter S, Ludwig RL, Vousden KH |date=November 2011 |title=Regulation of p53 stability and function by the deubiquitinating enzyme USP42 |journal=The EMBO Journal |volume=30 |issue=24 |pages=4921–30 |doi=10.1038/emboj.2011.419 |pmc=3243628 |pmid=22085928}}</ref> [[USP10]] operates primarily in the cytoplasm, where it counteracts MDM2 by directly deubiquitinating p53. After DNA damage, USP10 translocates to the nucleus and further stabilizes p53. It does not interact with MDM2.<ref name="pmid20096447" />

=== Post-translational modifications and cofactors === Phosphorylation of the N-terminus not only prevents MDM2 binding but also facilitates the recruitment of cofactors. [[Pin1]] enhances conformational changes in p53, while [[EP300|p300]] and [[PCAF]] acetylate the [[C-terminus]], exposing the DNA-binding domain and enhancing transcriptional activation. Conversely, deacetylases such as [[Sirt1]] and [[Sirt7]] remove these modifications, suppressing apoptosis and promoting cell survival.<ref name="pmid18239138">{{cite journal |vauthors=Vakhrusheva O, Smolka C, Gajawada P, Kostin S, Boettger T, Kubin T, Braun T, Bober E |date=March 2008 |title=Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice |journal=Circulation Research |volume=102 |issue=6 |pages=703–10 |doi=10.1161/CIRCRESAHA.107.164558 |pmid=18239138 |doi-access=free}}</ref> Some oncogenes can also activate p53 indirectly by inhibiting MDM2.<ref name="Inoue_2016">{{cite journal |vauthors=Inoue K, Fry EA, Frazier DP |date=April 2016 |title=Transcription factors that interact with p53 and Mdm2 |journal=International Journal of Cancer |volume=138 |issue=7 |pages=1577–85 |doi=10.1002/ijc.29663 |pmc=4698088 |pmid=26132471}}</ref>

=== Dynamics === Both experimental evidence and mathematical modeling indicate that p53 levels oscillate over time in response to cellular signals. These [[oscillation]]s become more pronounced in the presence of [[DNA damage]], such as [[double-stranded break]]s or UV exposure. Modeling approaches also help illustrate how mutations in p53 isoforms affect oscillatory behavior, potentially informing tissue-specific [[drug discovery|therapeutic development]].<ref name="Ribeiro_2007">{{cite journal |vauthors=Ribeiro AS, Charlebois DA, Lloyd-Price J |date=December 2007 |title=CellLine, a stochastic cell lineage simulator |journal=Bioinformatics |volume=23 |issue=24 |pages=3409–3411 |doi=10.1093/bioinformatics/btm491 |pmid=17928303 |doi-access=free}}</ref><ref name="Bullock_1997">{{cite journal |vauthors=Bullock AN, Henckel J, DeDecker BS, Johnson CM, Nikolova PV, Proctor MR, Lane DP, Fersht AR |date=December 1997 |title=Thermodynamic stability of wild-type and mutant p53 core domain |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=94 |issue=26 |pages=14338–42 |bibcode=1997PNAS...9414338B |doi=10.1073/pnas.94.26.14338 |pmc=24967 |pmid=9405613 |doi-access=free}}</ref><ref name="Explaining oscillations and variabi"/>

=== Epigenetics === p53 function is also influenced by [[chromatin]] environment. The corepressor [[TRIM24]] restricts p53 binding to epigenetically repressed loci by recognizing methylated histones. This interaction enables p53 to interpret local chromatin context and regulate gene expression in a locus-specific manner.<ref name="pmid37386214">{{cite journal |vauthors=Isbel L, Iskar M, Durdu S, Grand RS, Weiss J, Hietter-Pfeiffer E, Kozicka Z, Michael AK, Burger L, Thomä NH, Schübeler D |date=June 2023 |title=Readout of histone methylation by Trim24 locally restricts chromatin opening by p53 |journal=Nature Structural & Molecular Biology |volume=30 |issue=7 |pages=948–57 |doi=10.1038/s41594-023-01021-8 |hdl=2440/139184 |pmc=10352137 |pmid=37386214 |doi-access=free |hdl-access=free}}</ref>{{citation needed|date=November 2024}}<ref>{{Cite web |title=Li-Fraumeni syndrome: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/condition/li-fraumeni-syndrome/ |access-date=2026-02-16 |website=medlineplus.gov |language=en}}</ref>

== Role in disease == [[File:Signal transduction pathways.svg|300px|thumb|right|Overview of signal transduction pathways involved in [[apoptosis]]]] [[File:Anaplastic astrocytoma - p53 - very high mag.jpg|thumb|A [[micrograph]] showing cells with abnormal p53 expression (brown) in a brain tumor. [[immunostain|p53 immunostain]].]] If the ''TP53'' gene is damaged, its ability to suppress tumors is severely compromised. Individuals who inherit only one functional copy of ''TP53'' are predisposed to developing tumors in early adulthood, a condition known as [[Li–Fraumeni syndrome]].{{citation needed|date=November 2024}}

The ''TP53'' gene can also be altered by [[mutagen]]s—such as [[chemical substance|chemicals]], [[radiation]], or certain [[virus]]es—thereby increasing the likelihood of uncontrolled cell division. More than 50 percent of human [[tumor]]s harbor a [[mutation]] or [[genetic deletion|deletion]] of the ''TP53'' gene.<ref name="pmid1905840">{{cite journal |vauthors=Hollstein M, Sidransky D, Vogelstein B, Harris CC |date=July 1991 |title=p53 mutations in human cancers |url=https://zenodo.org/record/1230948 |journal=Science |volume=253 |issue=5015 |pages=49–53 |bibcode=1991Sci...253...49H |doi=10.1126/science.1905840 |pmid=1905840 |s2cid=38527914}}</ref> Loss of p53 function leads to genomic instability, frequently resulting in an [[aneuploidy]] phenotype.<ref>{{cite journal |vauthors=Schmitt CA, Fridman JS, Yang M, Baranov E, Hoffman RM, Lowe SW |date=April 2002 |title=Dissecting p53 tumor suppressor functions in vivo |journal=Cancer Cell |volume=1 |issue=3 |pages=289–98 |doi=10.1016/S1535-6108(02)00047-8 |pmid=12086865 |doi-access=free}}</ref>

Certain pathogens can also disrupt p53 activity. For example, [[human papillomavirus]] (HPV) produces the viral protein [[Papillomaviridae#E6|E6]], which binds to and inactivates p53. In conjunction with the HPV protein [[Papillomaviridae#E7|E7]], which inactivates the cell cycle regulator [[pRb]], this promotes repeated cell division, clinically presenting as [[wart]]s. High-risk HPV types, particularly types 16 and 18, can drive the progression from benign warts to low- or high-grade [[cervical dysplasia]], reversible precancerous lesions. Persistent cervical infection can lead to irreversible changes, including [[carcinoma in situ]] and invasive cervical cancer. These outcomes are primarily driven by viral integration into the host genome and the continued expression of the E6 and E7 oncoproteins.<ref name="pmid18086422">{{cite book |title=HIV-1: Molecular Biology and Pathogenesis |vauthors=Angeletti PC, Zhang L, Wood C |year=2008 |isbn=978-0-12-373601-7 |series=Advances in Pharmacology |volume=56 |pages=509–57 |chapter=The Viral Etiology of AIDS-Associated Malignancies |doi=10.1016/S1054-3589(07)56016-3 |pmc=2149907 |pmid=18086422}}</ref>

=== Mutations === Most p53 mutations are detected by DNA sequencing. However, it is known that single missense mutations can have a large spectrum from rather mild to very severe functional effects.<ref name="Bullock_1997" /> [[File:P53 mutant.jpg|thumb|Pathogenic mechanisms associated with p53 mutations:<ref name="ab">{{cite journal |vauthors=Butera A, Amelio I |date=July 2024 |title=Deciphering the significance of p53 mutant proteins |journal=Trends in Cell Biology |volume=35 |issue=3 |pages=258–268 |doi=10.1016/j.tcb.2024.06.003 |pmid=38960851 |doi-access=free}}{{Creative Commons text attribution notice|cc=by4|from this source=yes}}</ref> (A) Wild-type p53 forms homotetramers that activate gene expression. (B) Dominant-negative mutants form heterotetramers with wild-type p53, impairing transcription in heterozygous states (p53mut/+). (C) Loss-of-function arises from complete inactivation of wild-type alleles and inactivity of the mutant protein. (D) Gain-of-function mutations confer neomorphic activities, such as hijacking other transcription factors, promoting tumorigenesis. Abbreviation: WT, wild type.<ref name=ab/>]] The large spectrum of cancer phenotypes due to mutations in the ''TP53'' gene is also supported by the fact that different [[protein isoform|isoforms]] of p53 proteins have different cellular mechanisms for prevention against cancer. Mutations in ''TP53'' can give rise to different isoforms, preventing their overall functionality in different cellular mechanisms and thereby extending the cancer phenotype from mild to severe. Recent studies show that p53 isoforms are differentially expressed in different human tissues, and the [[mutation|loss-of-function or gain-of-function mutations]] within the isoforms can cause tissue-specific cancer or provide cancer [[stem cell]] [[cell potency|potential]] in different tissues.<ref name="Bourdon" /><ref name="pmid21779513">{{cite journal |vauthors=Khoury MP, Bourdon JC |date=April 2011 |title=p53 Isoforms: An Intracellular Microprocessor? |journal=Genes & Cancer |volume=2 |issue=4 |pages=453–65 |doi=10.1177/1947601911408893 |pmc=3135639 |pmid=21779513}}</ref><ref>{{cite journal |vauthors=Avery-Kiejda KA, Morten B, Wong-Brown MW, Mathe A, Scott RJ |date=March 2014 |title=The relative mRNA expression of p53 isoforms in breast cancer is associated with clinical features and outcome |journal=Carcinogenesis |volume=35 |issue=3 |pages=586–96 |doi=10.1093/carcin/bgt411 |pmid=24336193 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Arsic N, Gadea G, Lagerqvist EL, Busson M, Cahuzac N, Brock C, Hollande F, Gire V, Pannequin J, Roux P |date=April 2015 |title=The p53 isoform Δ133p53β promotes cancer stem cell potential |journal=Stem Cell Reports |volume=4 |issue=4 |pages=531–40 |doi=10.1016/j.stemcr.2015.02.001 |pmc=4400643 |pmid=25754205}}</ref> TP53 mutation also hits energy metabolism and increases glycolysis in breast cancer cells.<ref>{{cite journal |vauthors=Harami-Papp H, Pongor LS, Munkácsy G, Horváth G, Nagy ÁM, Ambrus A, Hauser P, Szabó A, Tretter L, Győrffy B |date=October 2016 |title=TP53 mutation hits energy metabolism and increases glycolysis in breast cancer |journal=Oncotarget |volume=7 |issue=41 |pages=67183–67195 |doi=10.18632/oncotarget.11594 |pmc=5341867 |pmid=27582538}}</ref>

==== Codon 72 variations ==== A common human [[polymorphism (biology)|polymorphism]] in ''TP53'' involves a substitution of [[arginine]] for [[proline]] at codon 72 of exon 4. Numerous studies have explored the relationship between this variation and cancer susceptibility, yielding mixed results. For instance, a 2009 meta-analysis found no association between the codon 72 polymorphism and cervical cancer risk.<ref name="pmid19625214">{{cite journal |vauthors=Klug SJ, Ressing M, Koenig J, Abba MC, Agorastos T, Brenna SM, Ciotti M, Das BR, Del Mistro A, Dybikowska A, Giuliano AR, Gudleviciene Z, Gyllensten U, Haws AL, Helland A, Herrington CS, Hildesheim A, Humbey O, Jee SH, Kim JW, Madeleine MM, Menczer J, Ngan HY, Nishikawa A, Niwa Y, Pegoraro R, Pillai MR, Ranzani G, Rezza G, Rosenthal AN, Roychoudhury S, Saranath D, Schmitt VM, Sengupta S, Settheetham-Ishida W, Shirasawa H, Snijders PJ, Stoler MH, Suárez-Rincón AE, Szarka K, Tachezy R, Ueda M, van der Zee AG, von Knebel Doeberitz M, Wu MT, Yamashita T, Zehbe I, Blettner M |date=August 2009 |title=TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies |journal=The Lancet. Oncology |volume=10 |issue=8 |pages=772–84 |doi=10.1016/S1470-2045(09)70187-1 |pmid=19625214}}</ref>

Other studies have identified possible associations between the codon 72 polymorphism and various cancers. A 2011 study reported that the proline variant significantly increased pancreatic cancer risk in males.<ref name="pmid21468597">{{cite journal |vauthors=Sonoyama T, Sakai A, Mita Y, Yasuda Y, Kawamoto H, Yagi T, Yoshioka M, Mimura T, Nakachi K, Ouchida M, Yamamoto K, Shimizu K |date=2011 |title=TP53 codon 72 polymorphism is associated with pancreatic cancer risk in males, smokers and drinkers |journal=Molecular Medicine Reports |volume=4 |issue=3 |pages=489–95 |doi=10.3892/mmr.2011.449 |pmid=21468597}}</ref> Another study found that proline homozygosity was associated with decreased breast cancer risk in Arab women.<ref name="pmid20443084">{{cite journal |vauthors=Alawadi S, Ghabreau L, Alsaleh M, Abdulaziz Z, Rafeek M, Akil N, Alkhalaf M |date=September 2011 |title=P53 gene polymorphisms and breast cancer risk in Arab women |journal=Medical Oncology |volume=28 |issue=3 |pages=709–15 |doi=10.1007/s12032-010-9505-4 |pmid=20443084 |s2cid=207372095}}</ref> Additional research suggested that ''TP53'' codon 72 polymorphisms, in combination with [[MDM2 SNP309]] and [[A2164G]], may affect susceptibility and age of onset for non-oropharyngeal cancers in women.<ref name="pmid21656578">{{cite journal |vauthors=Yu H, Huang YJ, Liu Z, Wang LE, Li G, Sturgis EM, Johnson DG, Wei Q |date=September 2011 |title=Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck |journal=Molecular Carcinogenesis |volume=50 |issue=9 |pages=697–706 |doi=10.1002/mc.20806 |pmc=3142329 |pmid=21656578}}</ref> A separate 2011 study linked the polymorphism to an increased risk of lung cancer in a Korean population.<ref name="pmid21316118">{{cite journal |vauthors=Piao JM, Kim HN, Song HR, Kweon SS, Choi JS, Yun WJ, Kim YC, Oh IJ, Kim KS, Shin MH |date=September 2011 |title=p53 codon 72 polymorphism and the risk of lung cancer in a Korean population |journal=Lung Cancer |volume=73 |issue=3 |pages=264–7 |doi=10.1016/j.lungcan.2010.12.017 |pmid=21316118}}</ref>

However, meta-analyses published in 2011 found no significant associations between the codon 72 variant and risks of either colorectal<ref name="pmid21140221">{{cite journal |vauthors=Wang JJ, Zheng Y, Sun L, Wang L, Yu PB, Dong JH, Zhang L, Xu J, Shi W, Ren YC |date=November 2011 |title=TP53 codon 72 polymorphism and colorectal cancer susceptibility: a meta-analysis |journal=Molecular Biology Reports |volume=38 |issue=8 |pages=4847–53 |doi=10.1007/s11033-010-0619-8 |pmid=21140221 |s2cid=11730631}}</ref> or endometrial cancer.<ref name="pmid20552298">{{cite journal |vauthors=Jiang DK, Yao L, Ren WH, Wang WZ, Peng B, Yu L |date=December 2011 |title=TP53 Arg72Pro polymorphism and endometrial cancer risk: a meta-analysis |journal=Medical Oncology |volume=28 |issue=4 |pages=1129–35 |doi=10.1007/s12032-010-9597-x |pmid=20552298 |s2cid=32990396}}</ref> A study of a Brazilian birth cohort found an association between the arginine variant and individuals without a family history of cancer.<ref name="pmid22116280">{{cite journal |vauthors=Thurow HS, Haack R, Hartwig FP, Oliveira IO, Dellagostin OA, Gigante DP, Horta BL, Collares T, Seixas FK |date=December 2011 |title=TP53 gene polymorphism: importance to cancer, ethnicity and birth weight in a Brazilian cohort |journal=Journal of Biosciences |volume=36 |issue=5 |pages=823–31 |doi=10.1007/s12038-011-9147-5 |pmid=22116280 |s2cid=23027087}}</ref> Meanwhile, another study reported that individuals with the homozygous Pro/Pro genotype had a significantly increased risk of renal cell carcinoma.<ref name="pmid21982800">{{cite journal |vauthors=Huang CY, Su CT, Chu JS, Huang SP, Pu YS, Yang HY, Chung CJ, Wu CC, Hsueh YM |date=December 2011 |title=The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area |journal=Toxicology and Applied Pharmacology |volume=257 |issue=3 |pages=349–55 |bibcode=2011ToxAP.257..349H |doi=10.1016/j.taap.2011.09.018 |pmid=21982800}}</ref>

=== Therapeutic reactivation and gene therapy === While increasing p53 levels might appear beneficial for treating cancer, sustained p53 activation can cause premature aging.<ref name="pmid11780111">{{cite journal |vauthors=Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A, Donehower LA |date=January 2002 |title=p53 mutant mice that display early ageing-associated phenotypes |journal=Nature |volume=415 |issue=6867 |pages=45–53 |bibcode=2002Natur.415...45T |doi=10.1038/415045a |pmid=11780111 |s2cid=749047}}</ref> A more promising approach involves restoring normal, [[endogenous]] p53 function. In some tumor types, this leads to regression via apoptosis or normalization of cell growth.<ref name="pmid17251932">{{cite journal |vauthors=Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T |date=February 2007 |title=Restoration of p53 function leads to tumour regression in vivo |journal=Nature |volume=445 |issue=7128 |pages=661–5 |doi=10.1038/nature05541 |pmid=17251932 |s2cid=4373520}}</ref><ref name="pmid24154492">{{cite journal |vauthors=Herce HD, Deng W, Helma J, Leonhardt H, Cardoso MC |year=2013 |title=Visualization and targeted disruption of protein interactions in living cells |journal=Nature Communications |volume=4 |bibcode=2013NatCo...4.2660H |doi=10.1038/ncomms3660 |pmc=3826628 |pmid=24154492 |article-number=2660}}</ref>

The first commercial gene therapy, [[Gendicine]], was approved in China in 2003 for [[head and neck squamous cell carcinoma]]. It delivers a functional copy of the ''TP53'' gene using a modified [[adenovirus]].<ref name="Gend">{{cite journal |vauthors=Pearson S, Jia H, Kandachi K |date=January 2004 |title=China approves first gene therapy |journal=Nature Biotechnology |volume=22 |issue=1 |pages=3–4 |doi=10.1038/nbt0104-3 |pmc=7097065 |pmid=14704685}}</ref>

The small-molecule inhibitor MI-63 can bind to [[MDM2]], blocking its interaction with p53 and reactivating p53 in cancers where its function is suppressed.<ref>{{cite journal |vauthors=Canner JA, Sobo M, Ball S, Hutzen B, DeAngelis S, Willis W, Studebaker AW, Ding K, Wang S, Yang D, Lin J |date=September 2009 |title=MI-63: a novel small-molecule inhibitor targets MDM2 and induces apoptosis in embryonal and alveolar rhabdomyosarcoma cells with wild-type p53 |journal=British Journal of Cancer |volume=101 |issue=5 |pages=774–81 |doi=10.1038/sj.bjc.6605199 |pmc=2736841 |pmid=19707204}}</ref>

A p53 reactivator [[rezatapopt]] is in clinical trials in patients whose tumors show the common Y220C mutation of p53, and restores anti-cancer effectiveness to the mutated protein.<ref>Chen S, Shepard HM, Lu M. Reactivating p53 mutants selectively in patients. ''Cancer Cell''. 2026 Apr 13;44(4):715-717. {{doi|10.1016/j.ccell.2026.03.009}} {{pmid|41932331}}</ref>

=== Diagnostic and prognostic significance ===

{| class="wikitable" | [[File:Patterns of p53 expression.png|right|340px]] This image shows different patterns of p53 expression in endometrial cancers on chromogenic [[immunohistochemistry]], whereof all except wild-type are variably termed abnormal/aberrant/mutation-type and are strongly predictive of an underlying TP53 mutation:<ref>{{cite journal |vauthors=Köbel M, Ronnett BM, Singh N, Soslow RA, Gilks CB, McCluggage WG |date=January 2019 |title=Interpretation of P53 Immunohistochemistry in Endometrial Carcinomas: Toward Increased Reproducibility |journal=International Journal of Gynecological Pathology |volume=38 |issue=Suppl 1 |pages=S123–S131 |doi=10.1097/PGP.0000000000000488 |pmc=6127005 |pmid=29517499}} {{CC-notice|cc=by4}}</ref> * '''Wild-type''', upper left: Endometrial endometrioid carcinoma showing normal wild-type pattern of p53 expression with variable proportion of tumor cell nuclei staining with variable intensity. Note, this wild-type pattern should not be reported as "positive," because this is ambiguous reporting language. * '''Overexpression''', upper right: Endometrial endometrioid carcinoma, grade 3, with overexpression, showing strong staining in virtually all tumor cell nuclei, much stronger compared with the internal control of fibroblasts in the center. Note, there is some cytoplasmic background indicating that this staining is quite strong but this should not be interpreted as abnormal cytoplasmic pattern. * '''Complete absence''', lower left: Endometrial serous carcinoma showing complete absence of p53 expression with internal control showing moderate to strong but variable staining. Note, wild-type pattern in normal atrophic glands at 12 and 6 o'clock. * '''Both cytoplasmic and nuclear''', lower right: Endometrial endometrioid carcinoma showing cytoplasmic p53 expression with internal control (stroma and normal endometrial glands) showing nuclear wild-type pattern. The cytoplasmic pattern is accompanied by nuclear staining of similar intensity. |} [[File:Expression of p53 in urothelial neoplasms.png|thumb|[[Immunohistochemistry]] for p53 can help distinguish a [[papillary urothelial neoplasm of low malignant potential]] (PUNLMP) from a low grade [[urothelial carcinoma]]. Overexpression is seen in 75% of low-grade urothelial carcinomas and only 10% of PUNLMP.<ref>Image is taken from following source, with some modification by Mikael Häggström, MD:<br />- {{cite journal |vauthors=Schallenberg S, Plage H, Hofbauer S, Furlano K, Weinberger S, Bruch PG |year=2023 |title=Altered p53/p16 expression is linked to urothelial carcinoma progression but largely unrelated to prognosis in muscle-invasive tumors. |journal=Acta Oncol |volume=62 |issue=12 |pages=1880–1889 |doi=10.1080/0284186X.2023.2277344 |pmid=37938166 |doi-access=free}}</ref><ref>{{cite journal |author=Kalantari MR, Ahmadnia H |year=2007 |title=P53 overexpression in bladder urothelial neoplasms: new aspect of World Health Organization/International Society of Urological Pathology classification. |url=https://journals.sbmu.ac.ir/urolj/index.php/uj/article/view/103/102 |journal=Urol J |volume=4 |issue=4 |pages=230–3 |pmid=18270948}}</ref>]]

== Discovery == p53 was identified in 1979 by [[Lionel Crawford]], [[David P. Lane]], [[Arnold J. Levine|Arnold Levine]], and [[Lloyd Old]], working at [[Imperial Cancer Research Fund]] (UK), [[Princeton University]]/UMDNJ (Cancer Institute of New Jersey), and [[Memorial Sloan Kettering Cancer Center]], respectively. It had been hypothesized to exist before as the target of the [[SV40]] virus, a strain that induced development of tumors. The name '''p53''' is in fact a misnomer, as it describes the apparent [[molecular mass]] measured when it was first discovered, though it was later realised this was an overestimate: the correct molecular mass is only 43.7 kDa.<ref>{{cite journal |vauthors=Levine AJ, Oren M |date=October 2009 |title=The first 30 years of p53: growing ever more complex |journal=Nature Reviews. Cancer |volume=9 |issue=10 |pages=749–758 |bibcode=2009NatRC...9..749L |doi=10.1038/nrc2723 |pmc=2771725 |pmid=19776744}}</ref>

The ''TP53'' gene from the mouse was first cloned by [[Peter Chumakov]] of the [[Academy of Sciences of the USSR]] in 1982,<ref name="pmid6295732">{{cite journal |vauthors=Chumakov PM, Iotsova VS, Georgiev GP |year=1982 |title=[Isolation of a plasmid clone containing the mRNA sequence for mouse nonviral T-antigen] |journal=Doklady Akademii Nauk SSSR |language=ru |volume=267 |issue=5 |pages=1272–5 |pmid=6295732}}</ref> and independently in 1983 by [[Moshe Oren]] in collaboration with [[David Givol]] ([[Weizmann Institute of Science]]).<ref name="pmid6296874">{{cite journal |vauthors=Oren M, Levine AJ |date=January 1983 |title=Molecular cloning of a cDNA specific for the murine p53 cellular tumor antigen |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=80 |issue=1 |pages=56–9 |bibcode=1983PNAS...80...56O |doi=10.1073/pnas.80.1.56 |pmc=393308 |pmid=6296874 |doi-access=free}}</ref><ref name="pmid6646235">{{cite journal |vauthors=Zakut-Houri R, Oren M, Bienz B, Lavie V, Hazum S, Givol D |year=1983 |title=A single gene and a pseudogene for the cellular tumour antigen p53 |journal=Nature |volume=306 |issue=5943 |pages=594–7 |bibcode=1983Natur.306..594Z |doi=10.1038/306594a0 |pmid=6646235 |s2cid=4325094}}</ref> The human ''TP53'' gene was cloned in 1984<ref name="pmid6396087" /> and the full length clone in 1985.<ref name="pmid4006916">{{cite journal |vauthors=Zakut-Houri R, Bienz-Tadmor B, Givol D, Oren M |date=May 1985 |title=Human p53 cellular tumor antigen: cDNA sequence and expression in COS cells |journal=The EMBO Journal |volume=4 |issue=5 |pages=1251–5 |doi=10.1002/j.1460-2075.1985.tb03768.x |pmc=554332 |pmid=4006916}}</ref>

It was initially presumed to be an [[oncogene]] due to the use of mutated [[cDNA]] following purification of tumor cell [[mRNA]]. Its role as a [[tumor suppressor gene]] was revealed in 1989 by [[Bert Vogelstein]] at the [[Johns Hopkins School of Medicine]] and [[Arnold J. Levine|Arnold Levine]] at Princeton University.<ref name="pmid2649981">{{cite journal |vauthors=Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, vanTuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B |date=April 1989 |title=Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas |journal=Science |volume=244 |issue=4901 |pages=217–21 |bibcode=1989Sci...244..217B |doi=10.1126/science.2649981 |pmid=2649981}}</ref><ref>{{cite journal |vauthors=Finlay CA, Hinds PW, Levine AJ |date=June 1989 |title=The p53 proto-oncogene can act as a suppressor of transformation |journal=Cell |volume=57 |issue=7 |pages=1083–93 |doi=10.1016/0092-8674(89)90045-7 |pmid=2525423 |doi-access=free}}</ref> p53 went on to be identified as a transcription factor by [[Guillermina Lozano]] working at [[MD Anderson Cancer Center]].<ref>{{cite journal |vauthors=Raycroft L, Wu HY, Lozano G |date=August 1990 |title=Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene |journal=Science |volume=249 |issue=4972 |pages=1049–1051 |bibcode=1990Sci...249.1049R |doi=10.1126/science.2144364 |pmc=2935288 |pmid=2144364}}</ref>

Warren Maltzman, of the Waksman Institute of Rutgers University first demonstrated that TP53 was responsive to DNA damage in the form of ultraviolet radiation.<ref name="pmid6092932">{{cite journal |vauthors=Maltzman W, Czyzyk L |date=September 1984 |title=UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells |journal=Molecular and Cellular Biology |volume=4 |issue=9 |pages=1689–94 |doi=10.1128/mcb.4.9.1689 |pmc=368974 |pmid=6092932}}</ref> In a series of publications in 1991–92, Michael Kastan of [[Johns Hopkins University]], reported that TP53 was a critical part of a signal transduction pathway that helped cells respond to DNA damage.<ref name="pmid8013425">{{cite journal |vauthors=Kastan MB, Kuerbitz SJ |date=December 1993 |title=Control of G1 arrest after DNA damage |journal=Environmental Health Perspectives |volume=101 |issue=Suppl 5 |pages=55–8 |doi=10.2307/3431842 |jstor=3431842 |pmc=1519427 |pmid=8013425}}</ref>

In 1993, p53 was voted ''molecule of the year'' by [[Science (journal)|''Science'']] magazine.<ref name="pmid8266084">{{cite journal |vauthors=Koshland DE |date=December 1993 |title=Molecule of the year |journal=Science |volume=262 |issue=5142 |page=1953 |bibcode=1993Sci...262.1953K |doi=10.1126/science.8266084 |pmid=8266084}}</ref>

== Interactions == p53 has been shown to [[Protein-protein interaction|interact]] with: {{div col|colwidth=20em}} * [[Multisynthetase complex auxiliary component p38|AIMP2]],<ref name="pmid18695251">{{cite journal |vauthors=Han JM, Park BJ, Park SG, Oh YS, Choi SJ, Lee SW, Hwang SK, Chang SH, Cho MH, Kim S |date=August 2008 |title=AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=105 |issue=32 |pages=11206–11 |bibcode=2008PNAS..10511206H |doi=10.1073/pnas.0800297105 |pmc=2516205 |pmid=18695251 |doi-access=free}}</ref> * [[ANKRD2]],<ref name = pmid15136035 /> * [[Aprataxin|APTX]],<ref name = pmid15044383 /> * [[Ataxia telangiectasia mutated|ATM]],<ref name="Fabbro_2004">{{cite journal |vauthors=Fabbro M, Savage K, Hobson K, Deans AJ, Powell SN, McArthur GA, Khanna KK |date=July 2004 |title=BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage |journal=The Journal of Biological Chemistry |volume=279 |issue=30 |pages=31251–8 |doi=10.1074/jbc.M405372200 |pmid=15159397 |doi-access=free}}</ref><ref name = pmid10608806 /><ref name="pmid15632067">{{cite journal |vauthors=Kang J, Ferguson D, Song H, Bassing C, Eckersdorff M, Alt FW, Xu Y |date=January 2005 |title=Functional interaction of H2AX, NBS1, and p53 in ATM-dependent DNA damage responses and tumor suppression |journal=Molecular and Cellular Biology |volume=25 |issue=2 |pages=661–70 |doi=10.1128/MCB.25.2.661-670.2005 |pmc=543410 |pmid=15632067}}</ref><ref name="pmid9843217">{{cite journal |vauthors=Khanna KK, Keating KE, Kozlov S, Scott S, Gatei M, Hobson K, Taya Y, Gabrielli B, Chan D, Lees-Miller SP, Lavin MF |date=December 1998 |title=ATM associates with and phosphorylates p53: mapping the region of interaction |journal=Nature Genetics |volume=20 |issue=4 |pages=398–400 |doi=10.1038/3882 |pmid=9843217 |s2cid=23994762}}</ref><ref name="pmid9135004">{{cite journal |vauthors=Westphal CH, Schmaltz C, Rowan S, Elson A, Fisher DE, Leder P |date=May 1997 |title=Genetic interactions between atm and p53 influence cellular proliferation and irradiation-induced cell cycle checkpoints |journal=Cancer Research |volume=57 |issue=9 |pages=1664–7 |pmid=9135004}}</ref> * [[Ataxia telangiectasia and Rad3 related|ATR]],<ref name="Fabbro_2004" /><ref name="pmid10608806">{{cite journal |vauthors=Kim ST, Lim DS, Canman CE, Kastan MB |date=December 1999 |title=Substrate specificities and identification of putative substrates of ATM kinase family members |journal=The Journal of Biological Chemistry |volume=274 |issue=53 |pages=37538–43 |doi=10.1074/jbc.274.53.37538 |pmid=10608806 |doi-access=free}}</ref> * [[ATF3]],<ref name="pmid16169070">{{cite journal |vauthors=Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE |date=September 2005 |title=A human protein-protein interaction network: a resource for annotating the proteome |journal=Cell |volume=122 |issue=6 |pages=957–68 |bibcode=2005Cell..122..957S |doi=10.1016/j.cell.2005.08.029 |hdl=11858/00-001M-0000-0010-8592-0 |pmid=16169070 |doi-access=free |hdl-access=free}}</ref><ref name="pmid11792711">{{cite journal |vauthors=Yan C, Wang H, Boyd DD |date=March 2002 |title=ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter |journal=The Journal of Biological Chemistry |volume=277 |issue=13 |pages=10804–12 |doi=10.1074/jbc.M112069200 |pmid=11792711 |doi-access=free}}</ref> * [[Aurora A kinase|AURKA]],<ref name="pmid12198151">{{cite journal |vauthors=Chen SS, Chang PC, Cheng YW, Tang FM, Lin YS |date=September 2002 |title=Suppression of the STK15 oncogenic activity requires a transactivation-independent p53 function |journal=The EMBO Journal |volume=21 |issue=17 |pages=4491–9 |doi=10.1093/emboj/cdf409 |pmc=126178 |pmid=12198151}}</ref> * [[BAK1]],<ref name="pmid15077116">{{cite journal |vauthors=Leu JI, Dumont P, Hafey M, Murphy ME, George DL |date=May 2004 |title=Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex |journal=Nature Cell Biology |volume=6 |issue=5 |pages=443–50 |doi=10.1038/ncb1123 |pmid=15077116 |s2cid=43063712}}</ref> * [[BARD1]],<ref name = pmid14636569 /> * [[Bloom syndrome protein|BLM]],<ref name = pmid15364958 /><ref name="pmid11399766">{{cite journal |vauthors=Wang XW, Tseng A, Ellis NA, Spillare EA, Linke SP, Robles AI, Seker H, Yang Q, Hu P, Beresten S, Bemmels NA, Garfield S, Harris CC |date=August 2001 |title=Functional interaction of p53 and BLM DNA helicase in apoptosis |journal=The Journal of Biological Chemistry |volume=276 |issue=35 |pages=32948–55 |doi=10.1074/jbc.M103298200 |pmid=11399766 |doi-access=free}}</ref><ref name="pmid11781842">{{cite journal |vauthors=Garkavtsev IV, Kley N, Grigorian IA, Gudkov AV |date=December 2001 |title=The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control |journal=Oncogene |volume=20 |issue=57 |pages=8276–80 |doi=10.1038/sj.onc.1205120 |pmid=11781842 |s2cid=13084911}}</ref><ref name = pmid12080066 /> * [[BRCA1]],<ref name = pmid14636569 /><ref name="pmid14710355">{{cite journal |vauthors=Abramovitch S, Werner H |year=2003 |title=Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene |journal=Hormone and Metabolic Research |volume=35 |issue=11–12 |pages=758–62 |doi=10.1055/s-2004-814154 |pmid=14710355 |s2cid=20898175}}</ref><ref name="pmid9482880">{{cite journal |vauthors=Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H |date=March 1998 |title=BRCA1 regulates p53-dependent gene expression |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=95 |issue=5 |pages=2302–6 |bibcode=1998PNAS...95.2302O |doi=10.1073/pnas.95.5.2302 |pmc=19327 |pmid=9482880 |doi-access=free}}</ref><ref name="pmid9926942">{{cite journal |vauthors=Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN |date=January 1999 |title=The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter |journal=Oncogene |volume=18 |issue=1 |pages=263–8 |doi=10.1038/sj.onc.1202323 |pmid=9926942 |s2cid=7462625}}</ref><ref name="pmid9582019">{{cite journal |vauthors=Zhang H, Somasundaram K, Peng Y, Tian H, Zhang H, Bi D, Weber BL, El-Deiry WS |date=April 1998 |title=BRCA1 physically associates with p53 and stimulates its transcriptional activity |journal=Oncogene |volume=16 |issue=13 |pages=1713–21 |doi=10.1038/sj.onc.1201932 |pmid=9582019 |s2cid=24616900}}</ref> * [[BRCA2]],<ref name = pmid14636569 /><ref name="pmid9811893">{{cite journal |vauthors=Marmorstein LY, Ouchi T, Aaronson SA |date=November 1998 |title=The BRCA2 gene product functionally interacts with p53 and RAD51 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=95 |issue=23 |pages=13869–74 |bibcode=1998PNAS...9513869M |doi=10.1073/pnas.95.23.13869 |pmc=24938 |pmid=9811893 |doi-access=free}}</ref> * [[BRCC3]],<ref name = pmid14636569 /> * [[BRE (gene)|BRE]],<ref name="pmid14636569">{{cite journal |vauthors=Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R |date=November 2003 |title=Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair |journal=Molecular Cell |volume=12 |issue=5 |pages=1087–99 |doi=10.1016/S1097-2765(03)00424-6 |pmid=14636569 |doi-access=free}}</ref> * [[CCAAT/enhancer binding protein zeta|CEBPZ]],<ref name="pmid12534345">{{cite journal |vauthors=Uramoto H, Izumi H, Nagatani G, Ohmori H, Nagasue N, Ise T, Yoshida T, Yasumoto K, Kohno K |date=April 2003 |title=Physical interaction of tumour suppressor p53/p73 with CCAAT-binding transcription factor 2 (CTF2) and differential regulation of human high-mobility group 1 (HMG1) gene expression |journal=The Biochemical Journal |volume=371 |issue=Pt 2 |pages=301–10 |doi=10.1042/BJ20021646 |pmc=1223307 |pmid=12534345}}</ref> * [[CDC14A]],<ref name = pmid10644693 /> * [[Cdk1]],<ref name="pmid10884347">{{cite journal |vauthors=Luciani MG, Hutchins JR, Zheleva D, Hupp TR |date=July 2000 |title=The C-terminal regulatory domain of p53 contains a functional docking site for cyclin A |journal=Journal of Molecular Biology |volume=300 |issue=3 |pages=503–18 |doi=10.1006/jmbi.2000.3830 |pmid=10884347}}</ref><ref name="pmid11327730">{{cite journal |vauthors=Ababneh M, Götz C, Montenarh M |date=May 2001 |title=Downregulation of the cdc2/cyclin B protein kinase activity by binding of p53 to p34(cdc2) |journal=Biochemical and Biophysical Research Communications |volume=283 |issue=2 |pages=507–12 |doi=10.1006/bbrc.2001.4792 |pmid=11327730}}</ref> * [[CFLAR]],<ref name="pmid18559494">{{cite journal |vauthors=Abedini MR, Muller EJ, Brun J, Bergeron R, Gray DA, Tsang BK |date=June 2008 |title=Cisplatin induces p53-dependent FLICE-like inhibitory protein ubiquitination in ovarian cancer cells |journal=Cancer Research |volume=68 |issue=12 |pages=4511–7 |doi=10.1158/0008-5472.CAN-08-0673 |pmid=18559494 |doi-access=free}}</ref> * [[CHEK1]],<ref name="pmid15364958">{{cite journal |vauthors=Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, Halazonetis TD, Harris CC |date=September 2004 |title=Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest |journal=The Journal of Cell Biology |volume=166 |issue=6 |pages=801–13 |doi=10.1083/jcb.200405128 |pmc=2172115 |pmid=15364958}}</ref><ref name = pmid12756247 /><ref name="pmid11896572">{{cite journal |vauthors=Tian H, Faje AT, Lee SL, Jorgensen TJ |year=2002 |title=Radiation-induced phosphorylation of Chk1 at S345 is associated with p53-dependent cell cycle arrest pathways |journal=Neoplasia |volume=4 |issue=2 |pages=171–80 |doi=10.1038/sj.neo.7900219 |pmc=1550321 |pmid=11896572}}</ref> * [[CCNG1]],<ref name="pmid12556559">{{cite journal |vauthors=Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC, Quelle DE |date=January 2003 |title=Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways |journal=Molecular Cancer Research |volume=1 |issue=3 |pages=195–206 |pmid=12556559}}</ref> * [[CREB-binding protein|CREBBP]],<ref name="pmid12426395">{{cite journal |vauthors=Ito A, Kawaguchi Y, Lai CH, Kovacs JJ, Higashimoto Y, Appella E, Yao TP |date=November 2002 |title=MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation |journal=The EMBO Journal |volume=21 |issue=22 |pages=6236–45 |doi=10.1093/emboj/cdf616 |pmc=137207 |pmid=12426395}}</ref><ref name = pmid11782467 /><ref name = pmid10848610 /> * [[CREB1]],<ref name="pmid10848610">{{cite journal |vauthors=Giebler HA, Lemasson I, Nyborg JK |date=July 2000 |title=p53 recruitment of CREB binding protein mediated through phosphorylated CREB: a novel pathway of tumor suppressor regulation |journal=Molecular and Cellular Biology |volume=20 |issue=13 |pages=4849–58 |doi=10.1128/MCB.20.13.4849-4858.2000 |pmc=85936 |pmid=10848610}}</ref> * [[Cyclin H]],<ref name="pmid9840937">{{cite journal |vauthors=Schneider E, Montenarh M, Wagner P |date=November 1998 |title=Regulation of CAK kinase activity by p53 |journal=Oncogene |volume=17 |issue=21 |pages=2733–41 |doi=10.1038/sj.onc.1202504 |pmid=9840937 |s2cid=6281777}}</ref> * [[Cyclin-dependent kinase 7|CDK7]],<ref name = pmid9840937 /><ref name="pmid9372954">{{cite journal |vauthors=Ko LJ, Shieh SY, Chen X, Jayaraman L, Tamai K, Taya Y, Prives C, Pan ZQ |date=December 1997 |title=p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner |journal=Molecular and Cellular Biology |volume=17 |issue=12 |pages=7220–9 |doi=10.1128/mcb.17.12.7220 |pmc=232579 |pmid=9372954}}</ref> * [[DNA-PKcs]],<ref name = pmid10608806 /><ref name="pmid12756247">{{cite journal |vauthors=Goudelock DM, Jiang K, Pereira E, Russell B, Sanchez Y |date=August 2003 |title=Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex |journal=The Journal of Biological Chemistry |volume=278 |issue=32 |pages=29940–7 |doi=10.1074/jbc.M301765200 |pmid=12756247 |doi-access=free}}</ref><ref name="pmid9679063">{{cite journal |vauthors=Yavuzer U, Smith GC, Bliss T, Werner D, Jackson SP |date=July 1998 |title=DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D |journal=Genes & Development |volume=12 |issue=14 |pages=2188–99 |doi=10.1101/gad.12.14.2188 |pmc=317006 |pmid=9679063}}</ref> * [[E4F1]],<ref name="pmid12446718">{{cite journal |vauthors=Rizos H, Diefenbach E, Badhwar P, Woodruff S, Becker TM, Rooney RJ, Kefford RF |date=February 2003 |title=Association of p14ARF with the p120E4F transcriptional repressor enhances cell cycle inhibition |journal=The Journal of Biological Chemistry |volume=278 |issue=7 |pages=4981–9 |doi=10.1074/jbc.M210978200 |pmid=12446718 |doi-access=free}}</ref><ref name="pmid10644996">{{cite journal |vauthors=Sandy P, Gostissa M, Fogal V, Cecco LD, Szalay K, Rooney RJ, Schneider C, Del Sal G |date=January 2000 |title=p53 is involved in the p120E4F-mediated growth arrest |journal=Oncogene |volume=19 |issue=2 |pages=188–99 |doi=10.1038/sj.onc.1203250 |pmid=10644996 |doi-access=free}}</ref> * [[EFEMP2]],<ref name="pmid10380882">{{cite journal |vauthors=Gallagher WM, Argentini M, Sierra V, Bracco L, Debussche L, Conseiller E |date=June 1999 |title=MBP1: a novel mutant p53-specific protein partner with oncogenic properties |journal=Oncogene |volume=18 |issue=24 |pages=3608–16 |doi=10.1038/sj.onc.1202937 |pmid=10380882 |doi-access=free}}</ref> * [[Protein kinase R|EIF2AK2]],<ref name="pmid10348343">{{cite journal |vauthors=Cuddihy AR, Wong AH, Tam NW, Li S, Koromilas AE |date=April 1999 |title=The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro |journal=Oncogene |volume=18 |issue=17 |pages=2690–702 |doi=10.1038/sj.onc.1202620 |pmid=10348343 |s2cid=22467088}}</ref> * [[ELL (gene)|ELL]],<ref name="pmid10358050">{{cite journal |vauthors=Shinobu N, Maeda T, Aso T, Ito T, Kondo T, Koike K, Hatakeyama M |date=June 1999 |title=Physical interaction and functional antagonism between the RNA polymerase II elongation factor ELL and p53 |journal=The Journal of Biological Chemistry |volume=274 |issue=24 |pages=17003–10 |doi=10.1074/jbc.274.24.17003 |pmid=10358050 |doi-access=free}}</ref> * [[EP300]],<ref name="pmid11782467">{{cite journal |vauthors=Livengood JA, Scoggin KE, Van Orden K, McBryant SJ, Edayathumangalam RS, Laybourn PJ, Nyborg JK |date=March 2002 |title=p53 Transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300 |journal=The Journal of Biological Chemistry |volume=277 |issue=11 |pages=9054–61 |doi=10.1074/jbc.M108870200 |pmid=11782467 |doi-access=free}}</ref><ref name="pmid9809062">{{cite journal |vauthors=Grossman SR, Perez M, Kung AL, Joseph M, Mansur C, Xiao ZX, Kumar S, Howley PM, Livingston DM |date=October 1998 |title=p300/MDM2 complexes participate in MDM2-mediated p53 degradation |journal=Molecular Cell |volume=2 |issue=4 |pages=405–15 |doi=10.1016/S1097-2765(00)80140-9 |pmid=9809062 |doi-access=free}}</ref><ref name="pmid15186775">{{cite journal |vauthors=An W, Kim J, Roeder RG |date=June 2004 |title=Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53 |journal=Cell |volume=117 |issue=6 |pages=735–48 |doi=10.1016/j.cell.2004.05.009 |pmid=15186775 |doi-access=free}}</ref><ref name="pmid10942770">{{cite journal |vauthors=Pastorcic M, Das HK |date=November 2000 |title=Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene |journal=The Journal of Biological Chemistry |volume=275 |issue=45 |pages=34938–45 |doi=10.1074/jbc.M005411200 |pmid=10942770 |doi-access=free}}</ref> * [[ERCC6]],<ref name="pmid7663514">{{cite journal |vauthors=Wang XW, Yeh H, Schaeffer L, Roy R, Moncollin V, Egly JM, Wang Z, Freidberg EC, Evans MK, Taffe BG |date=June 1995 |title=p53 modulation of TFIIH-associated nucleotide excision repair activity |url=http://repub.eur.nl/pub/54884 |journal=Nature Genetics |volume=10 |issue=2 |pages=188–95 |doi=10.1038/ng0695-188 |hdl=1765/54884 |pmid=7663514 |s2cid=38325851 |hdl-access=free}}</ref><ref name="pmid10882116">{{cite journal |vauthors=Yu A, Fan HY, Liao D, Bailey AD, Weiner AM |date=May 2000 |title=Activation of p53 or loss of the Cockayne syndrome group B repair protein causes metaphase fragility of human U1, U2, and 5S genes |journal=Molecular Cell |volume=5 |issue=5 |pages=801–10 |doi=10.1016/S1097-2765(00)80320-2 |pmid=10882116 |doi-access=free}}</ref> * [[GNL3]],<ref name="pmid12464630">{{cite journal |vauthors=Tsai RY, McKay RD |date=December 2002 |title=A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells |journal=Genes & Development |volume=16 |issue=23 |pages=2991–3003 |doi=10.1101/gad.55671 |pmc=187487 |pmid=12464630}}</ref> * [[GPS2 (gene)|GPS2]],<ref name="pmid11486030">{{cite journal |vauthors=Peng YC, Kuo F, Breiding DE, Wang YF, Mansur CP, Androphy EJ |date=September 2001 |title=AMF1 (GPS2) modulates p53 transactivation |journal=Molecular and Cellular Biology |volume=21 |issue=17 |pages=5913–24 |doi=10.1128/MCB.21.17.5913-5924.2001 |pmc=87310 |pmid=11486030}}</ref> * [[GSK3B]],<ref name="pmid12048243">{{cite journal |vauthors=Watcharasit P, Bijur GN, Zmijewski JW, Song L, Zmijewska A, Chen X, Johnson GV, Jope RS |date=June 2002 |title=Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=99 |issue=12 |pages=7951–5 |bibcode=2002PNAS...99.7951W |doi=10.1073/pnas.122062299 |pmc=123001 |pmid=12048243 |doi-access=free}}</ref> * [[Heat shock protein 90kDa alpha (cytosolic), member A1|HSP90AA1]],<ref name = pmid11297531 /><ref name="pmid12427754">{{cite journal |vauthors=Wang C, Chen J |date=January 2003 |title=Phosphorylation and hsp90 binding mediate heat shock stabilization of p53 |journal=The Journal of Biological Chemistry |volume=278 |issue=3 |pages=2066–71 |doi=10.1074/jbc.M206697200 |pmid=12427754 |doi-access=free}}</ref><ref name="pmid11507088">{{cite journal |vauthors=Peng Y, Chen L, Li C, Lu W, Chen J |date=November 2001 |title=Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization |journal=The Journal of Biological Chemistry |volume=276 |issue=44 |pages=40583–90 |doi=10.1074/jbc.M102817200 |pmid=11507088 |doi-access=free}}</ref> * [[HIF1A]],<ref name="pmid12606552">{{cite journal |vauthors=Chen D, Li M, Luo J, Gu W |date=April 2003 |title=Direct interactions between HIF-1 alpha and Mdm2 modulate p53 function |journal=The Journal of Biological Chemistry |volume=278 |issue=16 |pages=13595–8 |doi=10.1074/jbc.C200694200 |pmid=12606552 |doi-access=free}}</ref><ref name="pmid10640274">{{cite journal |vauthors=Ravi R, Mookerjee B, Bhujwalla ZM, Sutter CH, Artemov D, Zeng Q, Dillehay LE, Madan A, Semenza GL, Bedi A |date=January 2000 |title=Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha |journal=Genes & Development |volume=14 |issue=1 |pages=34–44 |doi=10.1101/gad.14.1.34 |pmc=316350 |pmid=10640274}}</ref><ref name="pmid12124396">{{cite journal |vauthors=Hansson LO, Friedler A, Freund S, Rudiger S, Fersht AR |date=August 2002 |title=Two sequence motifs from HIF-1alpha bind to the DNA-binding site of p53 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=99 |issue=16 |pages=10305–9 |bibcode=2002PNAS...9910305H |doi=10.1073/pnas.122347199 |pmc=124909 |pmid=12124396 |doi-access=free}}</ref><ref name="pmid9537326">{{cite journal |vauthors=An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM |date=March 1998 |title=Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha |journal=Nature |volume=392 |issue=6674 |pages=405–8 |bibcode=1998Natur.392..405A |doi=10.1038/32925 |pmid=9537326 |s2cid=4423081}}</ref> * [[HIPK1]],<ref name="pmid12702766">{{cite journal |vauthors=Kondo S, Lu Y, Debbas M, Lin AW, Sarosi I, Itie A, Wakeham A, Tuan J, Saris C, Elliott G, Ma W, Benchimol S, Lowe SW, Mak TW, Thukral SK |date=April 2003 |title=Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase 1 (HIPK1) |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=100 |issue=9 |pages=5431–6 |bibcode=2003PNAS..100.5431K |doi=10.1073/pnas.0530308100 |pmc=154362 |pmid=12702766 |doi-access=free}}</ref> * [[HIPK2]],<ref name="pmid11740489">{{cite journal |vauthors=Hofmann TG, Möller A, Sirma H, Zentgraf H, Taya Y, Dröge W, Will H, Schmitz ML |date=January 2002 |title=Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2 |journal=Nature Cell Biology |volume=4 |issue=1 |pages=1–10 |doi=10.1038/ncb715 |pmid=11740489 |s2cid=37789883}}</ref><ref name="pmid11925430">{{cite journal |vauthors=Kim EJ, Park JS, Um SJ |date=August 2002 |title=Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo |journal=The Journal of Biological Chemistry |volume=277 |issue=35 |pages=32020–8 |doi=10.1074/jbc.M200153200 |pmid=11925430 |doi-access=free}}</ref> * [[HMGB1]],<ref name="pmid11106654">{{cite journal |vauthors=Imamura T, Izumi H, Nagatani G, Ise T, Nomoto M, Iwamoto Y, Kohno K |date=March 2001 |title=Interaction with p53 enhances binding of cisplatin-modified DNA by high mobility group 1 protein |journal=The Journal of Biological Chemistry |volume=276 |issue=10 |pages=7534–40 |doi=10.1074/jbc.M008143200 |pmid=11106654 |doi-access=free}}</ref><ref name="pmid11748221">{{cite journal |vauthors=Dintilhac A, Bernués J |date=March 2002 |title=HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences |journal=The Journal of Biological Chemistry |volume=277 |issue=9 |pages=7021–8 |doi=10.1074/jbc.M108417200 |hdl=10261/112516 |pmid=11748221 |doi-access=free |hdl-access=free}}</ref> * [[HSPA9]],<ref name="pmid11900485">{{cite journal |vauthors=Wadhwa R, Yaguchi T, Hasan MK, Mitsui Y, Reddel RR, Kaul SC |date=April 2002 |title=Hsp70 family member, mot-2/mthsp70/GRP75, binds to the cytoplasmic sequestration domain of the p53 protein |journal=Experimental Cell Research |volume=274 |issue=2 |pages=246–53 |doi=10.1006/excr.2002.5468 |pmid=11900485}}</ref> * [[Huntingtin]],<ref name="pmid10823891">{{cite journal |vauthors=Steffan JS, Kazantsev A, Spasic-Boskovic O, Greenwald M, Zhu YZ, Gohler H, Wanker EE, Bates GP, Housman DE, Thompson LM |date=June 2000 |title=The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=97 |issue=12 |pages=6763–8 |bibcode=2000PNAS...97.6763S |doi=10.1073/pnas.100110097 |pmc=18731 |pmid=10823891 |doi-access=free}}</ref> * [[ING1]],<ref name="pmid12208736">{{cite journal |vauthors=Leung KM, Po LS, Tsang FC, Siu WY, Lau A, Ho HT, Poon RY |date=September 2002 |title=The candidate tumor suppressor ING1b can stabilize p53 by disrupting the regulation of p53 by MDM2 |journal=Cancer Research |volume=62 |issue=17 |pages=4890–3 |pmid=12208736}}</ref><ref name="pmid9440695">{{cite journal |vauthors=Garkavtsev I, Grigorian IA, Ossovskaya VS, Chernov MV, Chumakov PM, Gudkov AV |date=January 1998 |title=The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control |journal=Nature |volume=391 |issue=6664 |pages=295–8 |bibcode=1998Natur.391..295G |doi=10.1038/34675 |pmid=9440695 |s2cid=4429461}}</ref> * [[ING4]],<ref name = pmid12750254 /><ref name="pmid18775696">{{cite journal |vauthors=Tsai KW, Tseng HC, Lin WC |date=October 2008 |title=Two wobble-splicing events affect ING4 protein subnuclear localization and degradation |journal=Experimental Cell Research |volume=314 |issue=17 |pages=3130–41 |doi=10.1016/j.yexcr.2008.08.002 |pmid=18775696}}</ref> * [[ING5]],<ref name="pmid12750254">{{cite journal |vauthors=Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S, Onogi H, Higashimoto Y, Appella E, Yokota J, Harris CC |date=May 2003 |title=p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity |journal=Cancer Research |volume=63 |issue=10 |pages=2373–8 |pmid=12750254}}</ref> * [[IκBα]],<ref name="pmid11799106">{{cite journal |vauthors=Chang NS |date=March 2002 |title=The non-ankyrin C terminus of Ikappa Balpha physically interacts with p53 in vivo and dissociates in response to apoptotic stress, hypoxia, DNA damage, and transforming growth factor-beta 1-mediated growth suppression |journal=The Journal of Biological Chemistry |volume=277 |issue=12 |pages=10323–31 |doi=10.1074/jbc.M106607200 |pmid=11799106 |doi-access=free}}</ref> * [[KPNB1]],<ref name="pmid11297531">{{cite journal |vauthors=Akakura S, Yoshida M, Yoneda Y, Horinouchi S |date=May 2001 |title=A role for Hsc70 in regulating nucleocytoplasmic transport of a temperature-sensitive p53 (p53Val-135) |journal=The Journal of Biological Chemistry |volume=276 |issue=18 |pages=14649–57 |doi=10.1074/jbc.M100200200 |pmid=11297531 |doi-access=free}}</ref> * [[LMO3]],<ref name="Larsen S, Yokochi T, Isogai E, Nakamura Y, Ozaki T, Nakagawara A 2010 252–7" /> * [[Mdm2]],<ref name = pmid12426395 /><ref name = pmid12915590 /><ref name = pmid12620407 /><ref name = pmid9529249 /> * [[MDM4]],<ref name="pmid12393902">{{cite journal |vauthors=Badciong JC, Haas AL |date=December 2002 |title=MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination |journal=The Journal of Biological Chemistry |volume=277 |issue=51 |pages=49668–75 |doi=10.1074/jbc.M208593200 |pmid=12393902 |doi-access=free}}</ref><ref name="pmid9226370">{{cite journal |vauthors=Shvarts A, Bazuine M, Dekker P, Ramos YF, Steegenga WT, Merckx G, van Ham RC, van der Houven van Oordt W, van der Eb AJ, Jochemsen AG |date=July 1997 |title=Isolation and identification of the human homolog of a new p53-binding protein, Mdmx |url=https://repository.ubn.ru.nl/bitstream/2066/142231/1/142231.pdf |journal=Genomics |volume=43 |issue=1 |pages=34–42 |doi=10.1006/geno.1997.4775 |hdl=2066/142231 |pmid=9226370 |s2cid=11794685 |hdl-access=free}}</ref> * [[MED1]],<ref name="pmid11118038">{{cite journal |vauthors=Frade R, Balbo M, Barel M |date=December 2000 |title=RB18A, whose gene is localized on chromosome 17q12-q21.1, regulates in vivo p53 transactivating activity |journal=Cancer Research |volume=60 |issue=23 |pages=6585–9 |pmid=11118038}}</ref><ref name="pmid9444950">{{cite journal |vauthors=Drané P, Barel M, Balbo M, Frade R |date=December 1997 |title=Identification of RB18A, a 205 kDa new p53 regulatory protein which shares antigenic and functional properties with p53 |journal=Oncogene |volume=15 |issue=25 |pages=3013–24 |doi=10.1038/sj.onc.1201492 |pmid=9444950 |doi-access=free}}</ref> * [[Mitogen-activated protein kinase 9|MAPK9]],<ref name="pmid9393873">{{cite journal |vauthors=Hu MC, Qiu WR, Wang YP |date=November 1997 |title=JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases |journal=Oncogene |volume=15 |issue=19 |pages=2277–87 |doi=10.1038/sj.onc.1201401 |pmid=9393873 |doi-access=free}}</ref><ref name="pmid12384512">{{cite journal |vauthors=Lin Y, Khokhlatchev A, Figeys D, Avruch J |date=December 2002 |title=Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis |journal=The Journal of Biological Chemistry |volume=277 |issue=50 |pages=47991–8001 |doi=10.1074/jbc.M202630200 |pmid=12384512 |doi-access=free}}</ref> * [[MNAT1]],<ref name = pmid9372954 /> * [[NDN (gene)|NDN]],<ref name="pmid10347180">{{cite journal |vauthors=Taniura H, Matsumoto K, Yoshikawa K |date=June 1999 |title=Physical and functional interactions of neuronal growth suppressor necdin with p53 |journal=The Journal of Biological Chemistry |volume=274 |issue=23 |pages=16242–8 |doi=10.1074/jbc.274.23.16242 |pmid=10347180 |doi-access=free}}</ref> * [[Nucleolin|NCL]],<ref name="pmid12138209">{{cite journal |vauthors=Daniely Y, Dimitrova DD, Borowiec JA |date=August 2002 |title=Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation |journal=Molecular and Cellular Biology |volume=22 |issue=16 |pages=6014–22 |doi=10.1128/MCB.22.16.6014-6022.2002 |pmc=133981 |pmid=12138209}}</ref> * [[NUMB (gene)|NUMB]],<ref name="pmid18172499">{{cite journal |vauthors=Colaluca IN, Tosoni D, Nuciforo P, Senic-Matuglia F, Galimberti V, Viale G, Pece S, Di Fiore PP |date=January 2008 |title=NUMB controls p53 tumour suppressor activity |journal=Nature |volume=451 |issue=7174 |pages=76–80 |bibcode=2008Natur.451...76C |doi=10.1038/nature06412 |pmid=18172499 |s2cid=4431258}}</ref> * [[NF-κB]],<ref name=pmid20546595 /> * [[P16 (gene)|P16]],<ref name = pmid12446718 /><ref name="pmid9529249">{{cite journal |vauthors=Zhang Y, Xiong Y, Yarbrough WG |date=March 1998 |title=ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways |journal=Cell |volume=92 |issue=6 |pages=725–34 |doi=10.1016/S0092-8674(00)81401-4 |pmid=9529249 |doi-access=free}}</ref><ref name = pmid14612427 /> * [[PARC (gene)|PARC]],<ref name="pmid12526791">{{cite journal |vauthors=Nikolaev AY, Li M, Puskas N, Qin J, Gu W |date=January 2003 |title=Parc: a cytoplasmic anchor for p53 |journal=Cell |volume=112 |issue=1 |pages=29–40 |doi=10.1016/S0092-8674(02)01255-2 |pmid=12526791 |doi-access=free}}</ref> * [[PARP1]],<ref name="pmid15044383">{{cite journal |vauthors=Gueven N, Becherel OJ, Kijas AW, Chen P, Howe O, Rudolph JH, Gatti R, Date H, Onodera O, Taucher-Scholz G, Lavin MF |date=May 2004 |title=Aprataxin, a novel protein that protects against genotoxic stress |journal=Human Molecular Genetics |volume=13 |issue=10 |pages=1081–93 |doi=10.1093/hmg/ddh122 |pmid=15044383 |doi-access=free}}</ref><ref name="pmid9565608">{{cite journal |vauthors=Malanga M, Pleschke JM, Kleczkowska HE, Althaus FR |date=May 1998 |title=Poly(ADP-ribose) binds to specific domains of p53 and alters its DNA binding functions |journal=The Journal of Biological Chemistry |volume=273 |issue=19 |pages=11839–43 |doi=10.1074/jbc.273.19.11839 |pmid=9565608 |doi-access=free}}</ref> * [[PIAS1]],<ref name = pmid10380882 /><ref name="pmid11583632">{{cite journal |vauthors=Kahyo T, Nishida T, Yasuda H |date=September 2001 |title=Involvement of PIAS1 in the sumoylation of tumor suppressor p53 |journal=Molecular Cell |volume=8 |issue=3 |pages=713–8 |doi=10.1016/S1097-2765(01)00349-5 |pmid=11583632 |doi-access=free}}</ref> * [[CDC14B]],<ref name="pmid10644693">{{cite journal |vauthors=Li L, Ljungman M, Dixon JE |date=January 2000 |title=The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53 |journal=The Journal of Biological Chemistry |volume=275 |issue=4 |pages=2410–4 |doi=10.1074/jbc.275.4.2410 |pmid=10644693 |doi-access=free}}</ref> * [[PIN1]],<ref name="pmid12388558">{{cite journal |vauthors=Wulf GM, Liou YC, Ryo A, Lee SW, Lu KP |date=December 2002 |title=Role of Pin1 in the regulation of p53 stability and p21 transactivation, and cell cycle checkpoints in response to DNA damage |journal=The Journal of Biological Chemistry |volume=277 |issue=50 |pages=47976–9 |doi=10.1074/jbc.C200538200 |pmid=12388558 |doi-access=free}}</ref><ref name="pmid12397362">{{cite journal |vauthors=Zacchi P, Gostissa M, Uchida T, Salvagno C, Avolio F, Volinia S, Ronai Z, Blandino G, Schneider C, Del Sal G |date=October 2002 |title=The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults |journal=Nature |volume=419 |issue=6909 |pages=853–7 |bibcode=2002Natur.419..853Z |doi=10.1038/nature01120 |pmid=12397362 |s2cid=4311658}}</ref> * [[PLAGL1]],<ref name="pmid11360197">{{cite journal |vauthors=Huang SM, Schönthal AH, Stallcup MR |date=April 2001 |title=Enhancement of p53-dependent gene activation by the transcriptional coactivator Zac1 |journal=Oncogene |volume=20 |issue=17 |pages=2134–43 |doi=10.1038/sj.onc.1204298 |pmid=11360197 |s2cid=21331603}}</ref> * [[PLK3]],<ref name="pmid11551930">{{cite journal |vauthors=Xie S, Wu H, Wang Q, Cogswell JP, Husain I, Conn C, Stambrook P, Jhanwar-Uniyal M, Dai W |date=November 2001 |title=Plk3 functionally links DNA damage to cell cycle arrest and apoptosis at least in part via the p53 pathway |journal=The Journal of Biological Chemistry |volume=276 |issue=46 |pages=43305–12 |doi=10.1074/jbc.M106050200 |pmid=11551930 |doi-access=free}}</ref><ref name="pmid12242661">{{cite journal |vauthors=Bahassi EM, Conn CW, Myer DL, Hennigan RF, McGowan CH, Sanchez Y, Stambrook PJ |date=September 2002 |title=Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved in stress response pathways |journal=Oncogene |volume=21 |issue=43 |pages=6633–40 |doi=10.1038/sj.onc.1205850 |pmid=12242661 |s2cid=24106070}}</ref> * [[PRKRA]],<ref name="pmid9010216">{{cite journal |vauthors=Simons A, Melamed-Bessudo C, Wolkowicz R, Sperling J, Sperling R, Eisenbach L, Rotter V |date=January 1997 |title=PACT: cloning and characterization of a cellular p53 binding protein that interacts with Rb |journal=Oncogene |volume=14 |issue=2 |pages=145–55 |doi=10.1038/sj.onc.1200825 |pmid=9010216 |doi-access=free}}</ref> * [[Prohibitin|PHB]],<ref name="pmid14500729">{{cite journal |vauthors=Fusaro G, Dasgupta P, Rastogi S, Joshi B, Chellappan S |date=November 2003 |title=Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling |journal=The Journal of Biological Chemistry |volume=278 |issue=48 |pages=47853–61 |doi=10.1074/jbc.M305171200 |pmid=14500729 |doi-access=free}}</ref> * [[Promyelocytic leukemia protein|PML]],<ref name="pmid12915590">{{cite journal |vauthors=Kurki S, Latonen L, Laiho M |date=October 2003 |title=Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization |journal=Journal of Cell Science |volume=116 |issue=Pt 19 |pages=3917–25 |doi=10.1242/jcs.00714 |pmid=12915590 |doi-access=free}}</ref><ref name="pmid11080164">{{cite journal |vauthors=Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K, Pandolfi PP, Will H, Schneider C, Del Sal G |date=November 2000 |title=Regulation of p53 activity in nuclear bodies by a specific PML isoform |journal=The EMBO Journal |volume=19 |issue=22 |pages=6185–95 |doi=10.1093/emboj/19.22.6185 |pmc=305840 |pmid=11080164}}</ref><ref name="pmid11025664">{{cite journal |vauthors=Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Pandolfi PP |date=October 2000 |title=The function of PML in p53-dependent apoptosis |journal=Nature Cell Biology |volume=2 |issue=10 |pages=730–6 |doi=10.1038/35036365 |pmid=11025664 |s2cid=13480833}}</ref> * [[PSME3]],<ref name="pmid18309296">{{cite journal |vauthors=Zhang Z, Zhang R |date=March 2008 |title=Proteasome activator PA28 gamma regulates p53 by enhancing its MDM2-mediated degradation |journal=The EMBO Journal |volume=27 |issue=6 |pages=852–64 |doi=10.1038/emboj.2008.25 |pmc=2265109 |pmid=18309296}}</ref> * [[PTEN (gene)|PTEN]],<ref name="pmid12620407">{{cite journal |vauthors=Freeman DJ, Li AG, Wei G, Li HH, Kertesz N, Lesche R, Whale AD, Martinez-Diaz H, Rozengurt N, Cardiff RD, Liu X, Wu H |date=February 2003 |title=PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms |journal=Cancer Cell |volume=3 |issue=2 |pages=117–30 |doi=10.1016/S1535-6108(03)00021-7 |pmid=12620407 |doi-access=free}}</ref> * [[PTK2]],<ref name="pmid18206965">{{cite journal |vauthors=Lim ST, Chen XL, Lim Y, Hanson DA, Vo TT, Howerton K, Larocque N, Fisher SJ, Schlaepfer DD, Ilic D |date=January 2008 |title=Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation |journal=Molecular Cell |volume=29 |issue=1 |pages=9–22 |doi=10.1016/j.molcel.2007.11.031 |pmc=2234035 |pmid=18206965}}</ref> * [[PTTG1]],<ref name="pmid12355087">{{cite journal |vauthors=Bernal JA, Luna R, Espina A, Lázaro I, Ramos-Morales F, Romero F, Arias C, Silva A, Tortolero M, Pintor-Toro JA |date=October 2002 |title=Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis |journal=Nature Genetics |volume=32 |issue=2 |pages=306–11 |doi=10.1038/ng997 |pmid=12355087 |s2cid=1770399}}</ref> * [[RAD51]],<ref name = pmid14636569 /><ref name="pmid8617246">{{cite journal |vauthors=Stürzbecher HW, Donzelmann B, Henning W, Knippschild U, Buchhop S |date=April 1996 |title=p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction |journal=The EMBO Journal |volume=15 |issue=8 |pages=1992–2002 |doi=10.1002/j.1460-2075.1996.tb00550.x |pmc=450118 |pmid=8617246}}</ref><ref name="pmid9380510">{{cite journal |vauthors=Buchhop S, Gibson MK, Wang XW, Wagner P, Stürzbecher HW, Harris CC |date=October 1997 |title=Interaction of p53 with the human Rad51 protein |journal=Nucleic Acids Research |volume=25 |issue=19 |pages=3868–74 |doi=10.1093/nar/25.19.3868 |pmc=146972 |pmid=9380510}}</ref> * [[RCHY1]],<ref name="pmid12654245">{{cite journal |vauthors=Leng RP, Lin Y, Ma W, Wu H, Lemmers B, Chung S, Parant JM, Lozano G, Hakem R, Benchimol S |date=March 2003 |title=Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation |journal=Cell |volume=112 |issue=6 |pages=779–91 |doi=10.1016/S0092-8674(03)00193-4 |pmid=12654245 |doi-access=free}}</ref><ref name="pmid19043414">{{cite journal |vauthors=Sheng Y, Laister RC, Lemak A, Wu B, Tai E, Duan S, Lukin J, Sunnerhagen M, Srisailam S, Karra M, Benchimol S, Arrowsmith CH |date=December 2008 |title=Molecular basis of Pirh2-mediated p53 ubiquitylation |journal=Nature Structural & Molecular Biology |volume=15 |issue=12 |pages=1334–42 |doi=10.1038/nsmb.1521 |pmc=4075976 |pmid=19043414}}</ref> * [[RELA]],<ref name=pmid20546595 /> * [[Reprimo]]{{citation needed|date=March 2021}} * [[Replication protein A1|RPA1]],<ref name="pmid15489903">{{cite journal |vauthors=Romanova LY, Willers H, Blagosklonny MV, Powell SN |date=December 2004 |title=The interaction of p53 with replication protein A mediates suppression of homologous recombination |journal=Oncogene |volume=23 |issue=56 |pages=9025–33 |doi=10.1038/sj.onc.1207982 |pmid=15489903 |s2cid=23482723}}</ref><ref name="pmid11751427">{{cite journal |vauthors=Riva F, Zuco V, Vink AA, Supino R, Prosperi E |date=December 2001 |title=UV-induced DNA incision and proliferating cell nuclear antigen recruitment to repair sites occur independently of p53-replication protein A interaction in p53 wild type and mutant ovarian carcinoma cells |journal=Carcinogenesis |volume=22 |issue=12 |pages=1971–8 |doi=10.1093/carcin/22.12.1971 |pmid=11751427}}</ref> * [[RPL11]],<ref name="pmid14612427">{{cite journal |vauthors=Zhang Y, Wolf GW, Bhat K, Jin A, Allio T, Burkhart WA, Xiong Y |date=December 2003 |title=Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway |journal=Molecular and Cellular Biology |volume=23 |issue=23 |pages=8902–12 |doi=10.1128/MCB.23.23.8902-8912.2003 |pmc=262682 |pmid=14612427}}</ref> * [[S100B]],<ref name="pmid15178678">{{cite journal |vauthors=Lin J, Yang Q, Yan Z, Markowitz J, Wilder PT, Carrier F, Weber DJ |date=August 2004 |title=Inhibiting S100B restores p53 levels in primary malignant melanoma cancer cells |journal=The Journal of Biological Chemistry |volume=279 |issue=32 |pages=34071–7 |doi=10.1074/jbc.M405419200 |pmid=15178678 |doi-access=free}}</ref> * [[Small ubiquitin-related modifier 1|SUMO1]],<ref name="pmid10961991">{{cite journal |vauthors=Minty A, Dumont X, Kaghad M, Caput D |date=November 2000 |title=Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif |journal=The Journal of Biological Chemistry |volume=275 |issue=46 |pages=36316–23 |doi=10.1074/jbc.M004293200 |pmid=10961991 |doi-access=free}}</ref><ref name="pmid18583933">{{cite journal |vauthors=Ivanchuk SM, Mondal S, Rutka JT |date=June 2008 |title=p14ARF interacts with DAXX: effects on HDM2 and p53 |journal=Cell Cycle |volume=7 |issue=12 |pages=1836–50 |doi=10.4161/cc.7.12.6025 |pmid=18583933 |doi-access=free}}</ref> * [[SMARCA4]],<ref name = pmid11950834 /> * [[SMARCB1]],<ref name="pmid11950834">{{cite journal |vauthors=Lee D, Kim JW, Seo T, Hwang SG, Choi EJ, Choe J |date=June 2002 |title=SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription |journal=The Journal of Biological Chemistry |volume=277 |issue=25 |pages=22330–7 |doi=10.1074/jbc.M111987200 |pmid=11950834 |doi-access=free}}</ref> * [[SMN1]],<ref name="pmid11704667">{{cite journal |vauthors=Young PJ, Day PM, Zhou J, Androphy EJ, Morris GE, Lorson CL |date=January 2002 |title=A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy |journal=The Journal of Biological Chemistry |volume=277 |issue=4 |pages=2852–9 |doi=10.1074/jbc.M108769200 |pmid=11704667 |doi-access=free}}</ref> * [[STAT3]],<ref name="pmid20546595">{{cite journal |vauthors=Choy MK, Movassagh M, Siggens L, Vujic A, Goddard M, Sánchez A, Perkins N, Figg N, Bennett M, Carroll J, Foo R |date=June 2010 |title=High-throughput sequencing identifies STAT3 as the DNA-associated factor for p53-NF-kappaB-complex-dependent gene expression in human heart failure |journal=Genome Medicine |volume=2 |issue=6 |doi=10.1186/gm158 |pmc=2905097 |pmid=20546595 |doi-access=free |article-number=37}}</ref> * [[TATA binding protein|TBP]],<ref name="pmid1465435">{{cite journal |vauthors=Seto E, Usheva A, Zambetti GP, Momand J, Horikoshi N, Weinmann R, Levine AJ, Shenk T |date=December 1992 |title=Wild-type p53 binds to the TATA-binding protein and represses transcription |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=89 |issue=24 |pages=12028–32 |bibcode=1992PNAS...8912028S |doi=10.1073/pnas.89.24.12028 |pmc=50691 |pmid=1465435 |doi-access=free}}</ref><ref name="pmid10359315">{{cite journal |vauthors=Cvekl A, Kashanchi F, Brady JN, Piatigorsky J |date=June 1999 |title=Pax-6 interactions with TATA-box-binding protein and retinoblastoma protein |journal=Investigative Ophthalmology & Visual Science |volume=40 |issue=7 |pages=1343–50 |pmid=10359315}}</ref> * [[TFAP2A]],<ref name="pmid12226108">{{cite journal |vauthors=McPherson LA, Loktev AV, Weigel RJ |date=November 2002 |title=Tumor suppressor activity of AP2alpha mediated through a direct interaction with p53 |journal=The Journal of Biological Chemistry |volume=277 |issue=47 |pages=45028–33 |doi=10.1074/jbc.M208924200 |pmid=12226108 |doi-access=free}}</ref> * [[TFDP1]],<ref name="pmid8816502">{{cite journal |vauthors=Sørensen TS, Girling R, Lee CW, Gannon J, Bandara LR, La Thangue NB |date=October 1996 |title=Functional interaction between DP-1 and p53 |journal=Molecular and Cellular Biology |volume=16 |issue=10 |pages=5888–95 |doi=10.1128/mcb.16.10.5888 |pmc=231590 |pmid=8816502}}</ref> * [[C12orf5|TIGAR]],<ref name="pmid16839873">{{cite journal |vauthors=Green DR, Chipuk JE |date=July 2006 |title=p53 and metabolism: Inside the TIGAR |journal=Cell |volume=126 |issue=1 |pages=30–2 |doi=10.1016/j.cell.2006.06.032 |pmid=16839873 |doi-access=free}}</ref> * [[TOP1]],<ref name="pmid10468612">{{cite journal |vauthors=Gobert C, Skladanowski A, Larsen AK |date=August 1999 |title=The interaction between p53 and DNA topoisomerase I is regulated differently in cells with wild-type and mutant p53 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=96 |issue=18 |pages=10355–60 |bibcode=1999PNAS...9610355G |doi=10.1073/pnas.96.18.10355 |pmc=17892 |pmid=10468612 |doi-access=free}}</ref><ref name="pmid11805286">{{cite journal |vauthors=Mao Y, Mehl IR, Muller MT |date=February 2002 |title=Subnuclear distribution of topoisomerase I is linked to ongoing transcription and p53 status |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=99 |issue=3 |pages=1235–40 |bibcode=2002PNAS...99.1235M |doi=10.1073/pnas.022631899 |pmc=122173 |pmid=11805286 |doi-access=free}}</ref> * [[TOP2A]],<ref name = pmid10666337 /> * [[TP53BP1]],<ref name = pmid15364958 /><ref name="pmid12110597">{{cite journal |vauthors=Derbyshire DJ, Basu BP, Serpell LC, Joo WS, Date T, Iwabuchi K, Doherty AJ |date=July 2002 |title=Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor |journal=The EMBO Journal |volume=21 |issue=14 |pages=3863–72 |doi=10.1093/emboj/cdf383 |pmc=126127 |pmid=12110597}}</ref><ref name="pmid14978302">{{cite journal |vauthors=Ekblad CM, Friedler A, Veprintsev D, Weinberg RL, Itzhaki LS |date=March 2004 |title=Comparison of BRCT domains of BRCA1 and 53BP1: a biophysical analysis |journal=Protein Science |volume=13 |issue=3 |pages=617–25 |doi=10.1110/ps.03461404 |pmc=2286730 |pmid=14978302}}</ref><ref name="pmid15611139">{{cite journal |vauthors=Lo KW, Kan HM, Chan LN, Xu WG, Wang KP, Wu Z, Sheng M, Zhang M |date=March 2005 |title=The 8-kDa dynein light chain binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation |journal=The Journal of Biological Chemistry |volume=280 |issue=9 |pages=8172–9 |doi=10.1074/jbc.M411408200 |pmid=15611139 |doi-access=free}}</ref><ref name="pmid11877378">{{cite journal |vauthors=Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP |date=March 2002 |title=Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure |journal=Genes & Development |volume=16 |issue=5 |pages=583–93 |doi=10.1101/gad.959202 |pmc=155350 |pmid=11877378}}</ref><ref name="pmid12351827">{{cite journal |vauthors=Derbyshire DJ, Basu BP, Date T, Iwabuchi K, Doherty AJ |date=October 2002 |title=Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor |journal=Acta Crystallographica D |volume=58 |issue=Pt 10 Pt 2 |pages=1826–9 |bibcode=2002AcCrD..58.1826D |doi=10.1107/S0907444902010910 |pmid=12351827}}</ref><ref name = pmid8016121 /> * [[TP53BP2]],<ref name="pmid8016121">{{cite journal |vauthors=Iwabuchi K, Bartel PL, Li B, Marraccino R, Fields S |date=June 1994 |title=Two cellular proteins that bind to wild-type but not mutant p53 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=91 |issue=13 |pages=6098–102 |bibcode=1994PNAS...91.6098I |doi=10.1073/pnas.91.13.6098 |pmc=44145 |pmid=8016121 |doi-access=free}}</ref><ref name="pmid8668206">{{cite journal |vauthors=Naumovski L, Cleary ML |date=July 1996 |title=The p53-binding protein 53BP2 also interacts with Bc12 and impedes cell cycle progression at G2/M |journal=Molecular and Cellular Biology |volume=16 |issue=7 |pages=3884–92 |doi=10.1128/MCB.16.7.3884 |pmc=231385 |pmid=8668206}}</ref> * [[TOP2B]],<ref name="pmid10666337">{{cite journal |vauthors=Cowell IG, Okorokov AL, Cutts SA, Padget K, Bell M, Milner J, Austin CA |date=February 2000 |title=Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53 |journal=Experimental Cell Research |volume=255 |issue=1 |pages=86–94 |doi=10.1006/excr.1999.4772 |pmid=10666337}}</ref> * [[TP53INP1]],<ref name="pmid12851404">{{cite journal |vauthors=Tomasini R, Samir AA, Carrier A, Isnardon D, Cecchinelli B, Soddu S, Malissen B, Dagorn JC, Iovanna JL, Dusetti NJ |date=September 2003 |title=TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity |journal=The Journal of Biological Chemistry |volume=278 |issue=39 |pages=37722–9 |doi=10.1074/jbc.M301979200 |pmid=12851404 |doi-access=free}}</ref><ref name="pmid11511362">{{cite journal |vauthors=Okamura S, Arakawa H, Tanaka T, Nakanishi H, Ng CC, Taya Y, Monden M, Nakamura Y |date=July 2001 |title=p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis |journal=Molecular Cell |volume=8 |issue=1 |pages=85–94 |doi=10.1016/S1097-2765(01)00284-2 |pmid=11511362 |doi-access=free}}</ref> * [[TSG101]],<ref name="pmid11172000">{{cite journal |vauthors=Li L, Liao J, Ruland J, Mak TW, Cohen SN |date=February 2001 |title=A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=98 |issue=4 |pages=1619–24 |bibcode=2001PNAS...98.1619L |doi=10.1073/pnas.98.4.1619 |pmc=29306 |pmid=11172000 |doi-access=free}}</ref> * [[UBE2A]],<ref name="pmid12640129">{{cite journal |vauthors=Lyakhovich A, Shekhar MP |date=April 2003 |title=Supramolecular complex formation between Rad6 and proteins of the p53 pathway during DNA damage-induced response |journal=Molecular and Cellular Biology |volume=23 |issue=7 |pages=2463–75 |doi=10.1128/MCB.23.7.2463-2475.2003 |pmc=150718 |pmid=12640129}}</ref> * [[UBE2I]],<ref name = pmid10380882 /><ref name = pmid10961991 /><ref name="pmid8921390">{{cite journal |vauthors=Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ |date=October 1996 |title=Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system |url=https://zenodo.org/record/1229705 |journal=Genomics |volume=37 |issue=2 |pages=183–6 |doi=10.1006/geno.1996.0540 |pmid=8921390}}</ref><ref name="pmid11853669">{{cite journal |vauthors=Bernier-Villamor V, Sampson DA, Matunis MJ, Lima CD |date=February 2002 |title=Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1 |journal=Cell |volume=108 |issue=3 |pages=345–56 |bibcode=2002Cell..108..345B |doi=10.1016/S0092-8674(02)00630-X |pmid=11853669 |doi-access=free}}</ref> * [[Ubiquitin C|UBC]],<ref name = pmid18695251 /><ref name = pmid18309296 /><ref name = pmid18583933 /><ref name="pmid18632619">{{cite journal |vauthors=Sehat B, Andersson S, Girnita L, Larsson O |date=July 2008 |title=Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis |journal=Cancer Research |volume=68 |issue=14 |pages=5669–77 |doi=10.1158/0008-5472.CAN-07-6364 |pmid=18632619}}</ref><ref name="pmid18566590">{{cite journal |vauthors=Song MS, Song SJ, Kim SY, Oh HJ, Lim DS |date=July 2008 |title=The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex |journal=The EMBO Journal |volume=27 |issue=13 |pages=1863–74 |doi=10.1038/emboj.2008.115 |pmc=2486425 |pmid=18566590}}</ref><ref name="pmid18382127">{{cite journal |vauthors=Yang W, Dicker DT, Chen J, El-Deiry WS |date=March 2008 |title=CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing MDM2 |journal=Cell Cycle |volume=7 |issue=5 |pages=670–82 |doi=10.4161/cc.7.5.5701 |pmid=18382127 |doi-access=free}}</ref><ref name="pmid18359851">{{cite journal |vauthors=Abe Y, Oda-Sato E, Tobiume K, Kawauchi K, Taya Y, Okamoto K, Oren M, Tanaka N |date=March 2008 |title=Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=105 |issue=12 |pages=4838–43 |bibcode=2008PNAS..105.4838A |doi=10.1073/pnas.0712216105 |pmc=2290789 |pmid=18359851 |doi-access=free}}</ref><ref name="pmid18264029">{{cite journal |vauthors=Dohmesen C, Koeppel M, Dobbelstein M |date=January 2008 |title=Specific inhibition of Mdm2-mediated neddylation by Tip60 |journal=Cell Cycle |volume=7 |issue=2 |pages=222–31 |doi=10.4161/cc.7.2.5185 |pmid=18264029 |s2cid=8023403}}</ref> * [[USP7]],<ref name="pmid11923872">{{cite journal |vauthors=Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J, Gu W |date=April 2002 |title=Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization |journal=Nature |volume=416 |issue=6881 |pages=648–53 |bibcode=2002Natur.416..648L |doi=10.1038/nature737 |pmid=11923872 |s2cid=4389394}}</ref> * [[USP10]],<ref name="pmid20096447">{{cite journal |vauthors=Yuan J, Luo K, Zhang L, Cheville JC, Lou Z |date=February 2010 |title=USP10 Regulates p53 Localization and Stability by Deubiquitinating p53 |journal=Cell |volume=140 |issue=3 |pages=384–396 |doi=10.1016/j.cell.2009.12.032 |pmc=2820153 |pmid=20096447 |doi-access=free}}</ref> * [[Werner syndrome ATP-dependent helicase|WRN]],<ref name="pmid12080066">{{cite journal |vauthors=Yang Q, Zhang R, Wang XW, Spillare EA, Linke SP, Subramanian D, Griffith JD, Li JL, Hickson ID, Shen JC, Loeb LA, Mazur SJ, Appella E, Brosh RM, Karmakar P, Bohr VA, Harris CC |date=August 2002 |title=The processing of Holliday junctions by BLM and WRN helicases is regulated by p53 |journal=The Journal of Biological Chemistry |volume=277 |issue=35 |pages=31980–7 |doi=10.1074/jbc.M204111200 |hdl=10026.1/10341 |pmid=12080066 |doi-access=free |hdl-access=free}}</ref><ref name="pmid11427532">{{cite journal |vauthors=Brosh RM, Karmakar P, Sommers JA, Yang Q, Wang XW, Spillare EA, Harris CC, Bohr VA |date=September 2001 |title=p53 Modulates the exonuclease activity of Werner syndrome protein |journal=The Journal of Biological Chemistry |volume=276 |issue=37 |pages=35093–102 |doi=10.1074/jbc.M103332200 |pmid=11427532 |doi-access=free}}</ref> * [[WWOX]],<ref name="pmid11058590">{{cite journal |vauthors=Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, Zevotek N |date=February 2001 |title=Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity |journal=The Journal of Biological Chemistry |volume=276 |issue=5 |pages=3361–70 |doi=10.1074/jbc.M007140200 |pmid=11058590 |doi-access=free}}</ref> * [[XPB]],<ref name = pmid7663514 /> * [[Y box binding protein 1|YBX1]],<ref name="pmid15136035">{{cite journal |vauthors=Kojic S, Medeot E, Guccione E, Krmac H, Zara I, Martinelli V, Valle G, Faulkner G |date=May 2004 |title=The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle |journal=Journal of Molecular Biology |volume=339 |issue=2 |pages=313–25 |doi=10.1016/j.jmb.2004.03.071 |pmid=15136035}}</ref><ref name="pmid11175333">{{cite journal |vauthors=Okamoto T, Izumi H, Imamura T, Takano H, Ise T, Uchiumi T, Kuwano M, Kohno K |date=December 2000 |title=Direct interaction of p53 with the Y-box binding protein, YB-1: a mechanism for regulation of human gene expression |journal=Oncogene |volume=19 |issue=54 |pages=6194–202 |doi=10.1038/sj.onc.1204029 |pmid=11175333 |s2cid=19222684}}</ref> * [[YPEL3]],<ref name="pmid20388804">{{cite journal |vauthors=Kelley KD, Miller KR, Todd A, Kelley AR, Tuttle R, Berberich SJ |date=May 2010 |title=YPEL3, a p53-regulated gene that induces cellular senescence |journal=Cancer Research |volume=70 |issue=9 |pages=3566–75 |doi=10.1158/0008-5472.CAN-09-3219 |pmc=2862112 |pmid=20388804}}</ref> * [[YWHAZ]],<ref name="pmid9620776">{{cite journal |vauthors=Waterman MJ, Stavridi ES, Waterman JL, Halazonetis TD |date=June 1998 |title=ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins |journal=Nature Genetics |volume=19 |issue=2 |pages=175–8 |doi=10.1038/542 |pmid=9620776 |s2cid=26600934}}</ref> * [[Zif268]],<ref name="pmid11251186">{{cite journal |vauthors=Liu J, Grogan L, Nau MM, Allegra CJ, Chu E, Wright JJ |date=April 2001 |title=Physical interaction between p53 and primary response gene Egr-1 |journal=International Journal of Oncology |volume=18 |issue=4 |pages=863–70 |doi=10.3892/ijo.18.4.863 |pmid=11251186}}</ref> * [[ZNF148]],<ref name="pmid11416144">{{cite journal |vauthors=Bai L, Merchant JL |date=July 2001 |title=ZBP-89 promotes growth arrest through stabilization of p53 |journal=Molecular and Cellular Biology |volume=21 |issue=14 |pages=4670–83 |doi=10.1128/MCB.21.14.4670-4683.2001 |pmc=87140 |pmid=11416144}}</ref> * [[SIRT1]],<ref name="pmid19221490 ">{{cite journal |vauthors=Yamakuchi M, Lowenstein CJ |date=March 2009 |title=MiR-34, SIRT1 and p53: the feedback loop |journal=Cell Cycle |volume=8 |issue=5 |pages=712–5 |doi=10.4161/cc.8.5.7753 |pmid=19221490 |doi-access=free}}</ref> * circRNA_014511.<ref>{{cite journal |vauthors=Wang Y, Zhang J, Li J, Gui R, Nie X, Huang R |date=May 2019 |title=CircRNA_014511 affects the radiosensitivity of bone marrow mesenchymal stem cells by binding to miR-29b-2-5p |journal=Bosnian Journal of Basic Medical Sciences |volume=19 |issue=2 |pages=155–163 |doi=10.17305/bjbms.2019.3935 |pmc=6535393 |pmid=30640591}}</ref> {{div col end}}

==See also== * [[Eprenetapopt]], a reactivator of some mutant forms of p53 * [[Pifithrin]], an inhibitor of p53

== Notes == {{reflist|group=note}}

== References == {{reflist}}

== External links == {{Commons category|Tumor suppressor protein p53}} * {{cite web |title=p53 Knowledgebase |url=http://p53.bii.a-star.edu.sg/ |archive-url=https://web.archive.org/web/20060103170051/http://p53.bii.a-star.edu.sg/ |archive-date=2006-01-03 |access-date=2008-04-06 |publisher=Lane Group at the Institute of Molecular and Cell Biology (IMCB), Singapore}} * [https://www.ncbi.nlm.nih.gov/books/NBK1311/ GeneReviews/NCBI/NIH/UW entry on Li-Fraumeni Syndrome] * [https://web.archive.org/web/20090612192426/http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 TUMOR PROTEIN p53] @ [[OMIM]] * [http://www.news-medical.net/news/20130708/p53-restoration-of-function-drug-candidate-an-interview-with-Dr-Wayne-Danter-MD-FRCPC-President-and-CEO-of-Critical-Outcome-Technologies.aspx p53 restoration of function] * [http://atlasgeneticsoncology.org/Genes/P53ID88.html p53] @ The Atlas of Genetics and Cytogenetics in Oncology and Haematology * [https://www.genecards.org/cgi-bin/carddisp.pl?gene=tp53 TP53 Gene] @ GeneCards * [https://web.archive.org/web/20101124135159/http://insciences.org/articles.php?tag=p53 p53 News] provided by insciences organisation * {{cite web |date=2002-07-01 |title=p53 Tumor Suppressor |url=http://pdb101.rcsb.org/motm/31 |access-date=2008-04-06 |work=Molecule of the Month |publisher=RCSB Protein Data Bank |vauthors=Goodsel DS}} * {{cite web |title=p53 Web Site |url=http://p53.free.fr/ |access-date=2008-04-06 |vauthors=Soussi T}} * [https://livinglfs.org/ Living LFS] A non-profit Li-Fraumeni Syndrome patient support organization * [http://www.tp53.co.uk/ The George Pantziarka TP53 Trust] A support group from the UK for people with Li-Fraumeni Syndrome or other TP53-related disorders * [http://www-p53.iarc.fr/ IARC TP53 Somatic Mutations database] maintained at IARC, Lyon, by Magali Olivier * [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P04637 PDBe-KB] provides an overview of all the structure information available in the PDB for Human P53. * [https://www.youtube.com/watch?v=gY1p-xdHbQg|title= scientific animation] conformational changes of p53 upon binding to DNA

{{PDB Gallery|geneid=7157}} {{Transcription factors|g4}} {{Tumor suppressor genes and oncogenes}} {{Cell cycle proteins}}

[[Category:Programmed cell death]] [[Category:Proteins]] [[Category:Transcription factors]] [[Category:Tumor suppressor genes]] [[Category:Apoptosis]] [[Category:Genes mutated in mice]] [[Category:Aging-related proteins]]