ZFP36

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Tristetraprolin''' (TTP), also known as '''zinc finger protein 36 homolog''' (ZFP36), is a protein that in humans, mice and rats is encoded by the ''ZFP36'' gene.<ref name="pmid1699942">{{cite journal |vauthors=DuBois RN, McLane MW, Ryder K, Lau LF, Nathans D | title = A growth factor-inducible nuclear protein with a novel cysteine/histidine repetitive sequence | journal = J Biol Chem | volume = 265 | issue = 31 | pages = 19185–91 |date=Dec 1990 | doi = 10.1016/S0021-9258(17)30642-7 | pmid = 1699942 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ZFP36 zinc finger protein 36, C3H type, homolog (mouse)| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=7538}}</ref> It is a member of the TIS11 (TPA-induced sequence) family, along with butyrate response factors 1 and 2.<ref name="pmid21278925">{{cite journal |vauthors=Sanduja S, Blanco FF, Dixon DA | title = The roles of TTP and BRF proteins in regulated mRNA decay | journal = Wiley Interdiscip Rev RNA | volume = 2 | issue = 1 | pages = 42–57 | year = 2011 | pmid = 21278925 | pmc = 3030256 | doi = 10.1002/wrna.28 }}</ref>

TTP binds to AU-rich elements (AREs) in the 3'-untranslated regions (UTRs) of the mRNAs of some cytokines and promotes their degradation. For example, TTP is a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its mRNA.<ref name="pmid9703499">{{cite journal |vauthors=Carballo E, Lai WS, Blackshear PJ | title = Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin | journal = Science | volume = 281 | issue = 5379 | pages = 1001–5 |date=August 1998 | pmid = 9703499 | doi = 10.1126/science.281.5379.1001| bibcode = 1998Sci...281.1001C | url = https://zenodo.org/record/1231137}}</ref> Mice deficient in TTP develop a complex syndrome of inflammatory diseases.<ref name="pmid9703499"/>

==Interactions== ZFP36 has been shown to interact with 14-3-3 protein family members, such as YWHAH,<ref name="pmid11886850">{{cite journal |vauthors=Johnson BA, Stehn JR, Yaffe MB, Blackwell TK | title = Cytoplasmic localization of tristetraprolin involves 14-3-3-dependent and -independent mechanisms | journal = J. Biol. Chem. | volume = 277 | issue = 20 | pages = 18029–36 |date=May 2002 | pmid = 11886850 | doi = 10.1074/jbc.M110465200 | doi-access = free }}</ref> and with NUP214, a member of the nuclear pore complex.<ref name="pmid14766228">{{cite journal |vauthors=Carman JA, Nadler SG | title = Direct association of tristetraprolin with the nucleoporin CAN/Nup214 | journal = Biochem. Biophys. Res. Commun. | volume = 315 | issue = 2 | pages = 445–9 |date=March 2004 | pmid = 14766228 | doi = 10.1016/j.bbrc.2004.01.080 | bibcode = 2004BBRC..315..445C }}</ref>

==Regulation== Post-transcriptionally, TTP is regulated in several ways.<ref name="pmid21278925"/> The subcellular localization of TTP is influenced by interactions with protein partners such as the 14-3-3 family of proteins. These interactions and, possibly, interactions with target mRNAs are affected by the phosphorylation state of TTP, as the protein can be posttranslationally modified by a large number of protein kinases.<ref name="pmid21278925"/> There is some evidence that the TTP transcript may also be targeted by microRNAs, such as miR-29a.<ref name="pmid21278925"/>

== References == {{reflist}}

== Further reading == {{refbegin | 2}} *{{cite journal | author=Blackshear PJ |title=Tristetraprolin and other CCCH tandem zinc-finger proteins in the regulation of mRNA turnover |journal=Biochem. Soc. Trans. |volume=30 |issue= Pt 6 |pages= 945–52 |year= 2003 |pmid= 12440952 |doi= 10.1042/bst0300945}} *{{cite journal |vauthors=Carrick DM, Lai WS, Blackshear PJ |title=The tandem CCCH zinc finger protein tristetraprolin and its relevance to cytokine mRNA turnover and arthritis |journal=Arthritis Research & Therapy |volume=6 |issue= 6 |pages= 248–64 |year= 2005 |pmid= 15535838 |doi= 10.1186/ar1441 | pmc=1064869 |doi-access=free }} *{{cite journal | author=Taylor GA |title=The human TTP protein: sequence, alignment with related proteins, and chromosomal localization of the mouse and human genes |journal=Nucleic Acids Res. |volume=19 |issue= 12 |pages= 3454 |year= 1991 |pmid= 2062660 |doi=10.1093/nar/19.12.3454 | pmc=328350 |name-list-style=vanc| author2=Lai WS | author3=Oakey RJ | display-authors=3 | last4=Seldin | first4=Michael F. | last5=Shows | first5=Thomas B. | last6=Eddy | first6=Roger L. | last7=Blackshear | first7=Perry J. }} *{{cite journal |vauthors=Lai WS, Stumpo DJ, Blackshear PJ |title=Rapid insulin-stimulated accumulation of an mRNA encoding a proline-rich protein |journal=J. Biol. Chem. |volume=265 |issue= 27 |pages= 16556–63 |year= 1990 |doi=10.1016/S0021-9258(17)46259-4 |pmid= 2204625 |doi-access=free }} *{{cite journal |vauthors=Taylor GA, Thompson MJ, Lai WS, Blackshear PJ |title=Phosphorylation of tristetraprolin, a potential zinc finger transcription factor, by mitogen stimulation in intact cells and by mitogen-activated protein kinase in vitro |journal=J. Biol. Chem. |volume=270 |issue= 22 |pages= 13341–7 |year= 1995 |pmid= 7768935 |doi=10.1074/jbc.270.22.13341 |doi-access=free }} *{{cite journal |vauthors=Heximer SP, Forsdyke DR |title=A human putative lymphocyte G0/G1 switch gene homologous to a rodent gene encoding a zinc-binding potential transcription factor |journal=DNA Cell Biol. |volume=12 |issue= 1 |pages= 73–88 |year= 1993 |pmid= 8422274 |doi=10.1089/dna.1993.12.73 }} *{{cite journal | author=Huebner K |title=Chromosomal localization of four human zinc finger cDNAs |journal=Hum. Genet. |volume=91 |issue= 3 |pages= 217–22 |year= 1993 |pmid= 8478004 |doi=10.1007/BF00218259 |name-list-style=vanc| author2=Druck T | author3=LaForgia S | display-authors=3 | last4=Lasota | first4=Jerzy | last5=Croce | first5=Carlom. | last6=Lanfrancone | first6=Luisa | last7=Donti | first7=Emilio | last8=Pengue | first8=Gina | last9=Mantia | first9=Girolama |s2cid=35926610 }} *{{cite journal | author=Lai WS |title=Interactions of CCCH zinc finger proteins with mRNA. Binding of tristetraprolin-related zinc finger proteins to Au-rich elements and destabilization of mRNA |journal=J. Biol. Chem. |volume=275 |issue= 23 |pages= 17827–37 |year= 2000 |pmid= 10751406 |doi= 10.1074/jbc.M001696200 |name-list-style=vanc| author2=Carballo E | author3=Thorn JM | display-authors=3 | last4=Kennington | first4=EA | last5=Blackshear | first5=PJ |doi-access=free }} *{{cite journal |vauthors=Dintilhac A, Bernués J |title=HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences |journal=J. Biol. Chem. |volume=277 |issue= 9 |pages= 7021–8 |year= 2002 |pmid= 11748221 |doi= 10.1074/jbc.M108417200 |doi-access= free |hdl= 10261/112516 |hdl-access= free }} *{{cite journal |vauthors=Lai WS, Kennington EA, Blackshear PJ |title=Interactions of CCCH zinc finger proteins with mRNA: non-binding tristetraprolin mutants exert an inhibitory effect on degradation of AU-rich element-containing mRNAs |journal=J. Biol. Chem. |volume=277 |issue= 11 |pages= 9606–13 |year= 2002 |pmid= 11782475 |doi= 10.1074/jbc.M110395200 |doi-access= free }} *{{cite journal |vauthors=Johnson BA, Stehn JR, Yaffe MB, Blackwell TK |title=Cytoplasmic localization of tristetraprolin involves 14-3-3-dependent and -independent mechanisms |journal=J. Biol. Chem. |volume=277 |issue= 20 |pages= 18029–36 |year= 2002 |pmid= 11886850 |doi= 10.1074/jbc.M110465200 |doi-access= free }} *{{cite journal | author=Brooks SA |title=Analysis of the function, expression, and subcellular distribution of human tristetraprolin |journal=Arthritis Rheum. |volume=46 |issue= 5 |pages= 1362–70 |year= 2002 |pmid= 12115244 |doi= 10.1002/art.10235 |name-list-style=vanc| author2=Connolly JE | author3=Diegel RJ | display-authors=3 | last4=Fava | first4=Roy A. | last5=Rigby | first5=William F. C. |doi-access=free }} *{{cite journal | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |name-list-style=vanc| author2=Feingold EA | author3=Grouse LH | display-authors=3 | last4=Derge | first4=JG | last5=Klausner | first5=RD | last6=Collins | first6=FS | last7=Wagner | first7=L | last8=Shenmen | first8=CM | last9=Schuler | first9=GD |bibcode=2002PNAS...9916899M |doi-access=free }} *{{cite journal |vauthors=Amann BT, Worthington MT, Berg JM |title=A Cys3His zinc-binding domain from Nup475/tristetraprolin: a novel fold with a disklike structure |journal=Biochemistry |volume=42 |issue= 1 |pages= 217–21 |year= 2003 |pmid= 12515557 |doi= 10.1021/bi026988m }} *{{cite journal |vauthors=Yu H, Stasinopoulos S, Leedman P, Medcalf RL |title=Inherent instability of plasminogen activator inhibitor type 2 mRNA is regulated by tristetraprolin |journal=J. Biol. Chem. |volume=278 |issue= 16 |pages= 13912–8 |year= 2003 |pmid= 12578825 |doi= 10.1074/jbc.M213027200 |doi-access= free }} *{{cite journal |vauthors=Sawaoka H, Dixon DA, Oates JA, Boutaud O |title=Tristetraprolin binds to the 3'-untranslated region of cyclooxygenase-2 mRNA. A polyadenylation variant in a cancer cell line lacks the binding site |journal=J. Biol. Chem. |volume=278 |issue= 16 |pages= 13928–35 |year= 2003 |pmid= 12578839 |doi= 10.1074/jbc.M300016200 |doi-access= free }} {{refend}}