{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=3}} {{Infobox_gene}} '''Histone-binding protein RBBP4''' (also known as '''RbAp48''', or '''NURF55''') is a protein that in humans is encoded by the ''RBBP4'' gene.<ref name="pmid8350924">{{cite journal |vauthors=Qian YW, Wang YC, Hollingsworth RE Jr, Jones D, Ling N, Lee EY | title = A retinoblastoma-binding protein related to a negative regulator of Ras in yeast | journal = Nature | volume = 364 | issue = 6438 | pages = 648–52 |date=September 1993 | pmid = 8350924 | doi = 10.1038/364648a0 | bibcode = 1993Natur.364..648Q | s2cid = 4303062 }}</ref><ref name="pmid14609955">{{cite journal |vauthors=Barak O, Lazzaro MA, Lane WS, Speicher DW, Picketts DJ, Shiekhattar R | title = Isolation of human NURF: a regulator of Engrailed gene expression | journal = EMBO J | volume = 22 | issue = 22 | pages = 6089–100 |date=November 2003 | pmid = 14609955 | pmc = 275440 | doi = 10.1093/emboj/cdg582 }}</ref>
== Function == This gene encodes a ubiquitously expressed nuclear protein that belongs to a highly conserved subfamily of WD-repeat proteins. It is present in protein complexes involved in histone acetylation and chromatin assembly. It is part of the Mi-2/NuRD complex that has been implicated in chromatin remodeling and transcriptional repression associated with histone deacetylation. This encoded protein is also part of corepressor complexes, which is an integral component of transcriptional silencing. It is found among several cellular proteins that bind directly to retinoblastoma protein to regulate cell proliferation. This protein also seems to be involved in transcriptional repression of E2F-responsive genes.<ref name="entrez">{{cite web | title = Entrez Gene: RBBP4 retinoblastoma-binding protein 4| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=5928}}</ref>
== Clinical significance == A decrease of RbAp48 in the dentate gyrus (DG) of the hippocampus in the brain is suspected to be a main cause of memory loss in normal aging.<ref name="Pavlopoulos_2013">{{cite journal |vauthors=Pavlopoulos E, Jones S, Kosmidis S, Close M, Kim C, Kovalerchik O, Small SA, Kandel ER | title = Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48 | journal = Sci Transl Med | volume = 5 | issue = 200 | pages = 200ra115 |date=August 2013 | pmid = 23986399 | doi = 10.1126/scitranslmed.3006373 | pmc=4940031}}</ref> An age related decrease in RbAp48 is observed in the DG from human post-mortem tissue and also in mice. Furthermore, a gene knockin of a dominant negative form of RbAp48 causes memory deficits in young mice similar to that observed in older mice. Using lentiviral gene transfer to increase the expression of RbAp48 in the brain reverses memory deficits in older mice.<ref name="Pavlopoulos_2013"/>
RBBP4 works at least in part through the PKA-CREB1-CPB pathway.<ref name="Pavlopoulos_2013"/> Hence one possible therapeutic approach to restore age-related memory loss is the use of PKA-CREB1-CPB pathway stimulating drugs. It has previously been shown that dopamine D1/D5 agonists such as 6-Br-APB and SKF-38,393 that are positively coupled to adenylyl cyclase and the cAMP phosphodieserase inhibitor rolipram reduce memory defects in aged mice.<ref name="pmid10220457">{{cite journal |vauthors=Bach ME, Barad M, Son H, Zhuo M, Lu YF, Shih R, Mansuy I, Hawkins RD, Kandel ER | title = Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 9 | pages = 5280–5 |date=April 1999 | pmid = 10220457 | pmc = 21855 | doi = 10.1073/pnas.96.9.5280| bibcode = 1999PNAS...96.5280B | doi-access = free }}</ref>
==Interactions== RBBP4 has been shown to interact with: * BRCA1,<ref name = pmid10220405>{{cite journal |vauthors=Yarden RI, Brody LC | title = BRCA1 interacts with components of the histone deacetylase complex | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 9 | pages = 4983–8 | year = 1999 | pmid = 10220405 | pmc = 21803 | doi = 10.1073/pnas.96.9.4983| bibcode = 1999PNAS...96.4983Y | doi-access = free }}</ref> * CREBBP,<ref name = pmid10866654>{{cite journal |vauthors=Zhang Q, Vo N, Goodman RH | title = Histone binding protein RbAp48 interacts with a complex of CREB binding protein and phosphorylated CREB | journal = Mol. Cell. Biol. | volume = 20 | issue = 14 | pages = 4970–8 | year = 2000 | pmid = 10866654 | pmc = 85947 | doi = 10.1128/MCB.20.14.4970-4978.2000}}</ref> * GATAD2B,<ref name = pmid11756549>{{cite journal |vauthors=Feng Q, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Zhang Y | title = Identification and functional characterization of the p66/p68 components of the MeCP1 complex | journal = Mol. Cell. Biol. | volume = 22 | issue = 2 | pages = 536–46 | year = 2002 | pmid = 11756549 | pmc = 139742 | doi = 10.1128/MCB.22.2.536-546.2002}}</ref> * HDAC1,<ref name = pmid12943729>{{cite journal |vauthors=Zhang Y, Dufau ML | title = Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes | journal = J. Steroid Biochem. Mol. Biol. | volume = 85 | issue = 2–5 | pages = 401–14 | year = 2003 | pmid = 12943729 | doi = 10.1016/S0960-0760(03)00230-9| s2cid = 28512341 | url = https://zenodo.org/record/1260176 }}</ref><ref name = pmid12920132>{{cite journal |vauthors=Yao YL, Yang WM | title = The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity | journal = J. Biol. Chem. | volume = 278 | issue = 43 | pages = 42560–8 | year = 2003 | pmid = 12920132 | doi = 10.1074/jbc.M302955200 | doi-access = free }}</ref><ref name = pmid11470869>{{cite journal |vauthors=Nicolas E, Ait-Si-Ali S, Trouche D | title = The histone deacetylase HDAC3 targets RbAp48 to the retinoblastoma protein | journal = Nucleic Acids Res. | volume = 29 | issue = 15 | pages = 3131–6 | year = 2001 | pmid = 11470869 | pmc = 55834 | doi = 10.1093/nar/29.15.3131}}</ref><ref name = pmid10220385>{{cite journal |vauthors=Grozinger CM, Hassig CA, Schreiber SL | title = Three proteins define a class of human histone deacetylases related to yeast Hda1p | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 9 | pages = 4868–73 | year = 1999 | pmid = 10220385 | pmc = 21783 | doi = 10.1073/pnas.96.9.4868| bibcode = 1999PNAS...96.4868G | doi-access = free }}</ref><ref name = pmid11171972>{{cite journal |vauthors=You A, Tong JK, Grozinger CM, Schreiber SL | title = CoREST is an integral component of the CoREST- human histone deacetylase complex | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 4 | pages = 1454–8 | year = 2001 | pmid = 11171972 | pmc = 29278 | doi = 10.1073/pnas.98.4.1454 | bibcode = 2001PNAS...98.1454Y | doi-access = free }}</ref><ref name = pmid9150133>{{cite journal |vauthors=Hassig CA, Fleischer TC, Billin AN, Schreiber SL, Ayer DE | title = Histone deacetylase activity is required for full transcriptional repression by mSin3A | journal = Cell | volume = 89 | issue = 3 | pages = 341–7 | year = 1997 | pmid = 9150133 | doi = 10.1016/S0092-8674(00)80214-7| s2cid = 14233219 | doi-access = free }}</ref><ref name = pmid10471499>{{cite journal |vauthors=Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A | title = MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex | journal = Nat. Genet. | volume = 23 | issue = 1 | pages = 58–61 | year = 1999 | pmid = 10471499 | doi = 10.1038/12659 | hdl = 1842/684 | s2cid = 6147725 | hdl-access = free }}</ref><ref name = pmid10444591>{{cite journal |vauthors=Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D | title = Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation | journal = Genes Dev. | volume = 13 | issue = 15 | pages = 1924–35 | year = 1999 | pmid = 10444591 | pmc = 316920 | doi = 10.1101/gad.13.15.1924}}</ref><ref name = pmid12091390>{{cite journal |vauthors=Zhang Y, Dufau ML | title = Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex | journal = J. Biol. Chem. | volume = 277 | issue = 36 | pages = 33431–8 | year = 2002 | pmid = 12091390 | doi = 10.1074/jbc.M204417200 | doi-access = free }}</ref><ref name = pmid9520398>{{cite journal |vauthors=Hassig CA, Tong JK, Fleischer TC, Owa T, Grable PG, Ayer DE, Schreiber SL | title = A role for histone deacetylase activity in HDAC1-mediated transcriptional repression | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 7 | pages = 3519–24 | year = 1998 | pmid = 9520398 | pmc = 19868 | doi = 10.1073/pnas.95.7.3519| bibcode = 1998PNAS...95.3519H | doi-access = free }}</ref><ref name = pmid9150135>{{cite journal |vauthors=Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D | title = Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex | journal = Cell | volume = 89 | issue = 3 | pages = 357–64 | year = 1997 | pmid = 9150135 | doi = 10.1016/S0092-8674(00)80216-0| doi-access = free }}</ref> * HDAC2,<ref name = pmid12943729/><ref name = pmid12091390/><ref name = pmid12493763>{{cite journal |vauthors=Hakimi MA, Dong Y, Lane WS, Speicher DW, Shiekhattar R | title = A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes | journal = J. Biol. Chem. | volume = 278 | issue = 9 | pages = 7234–9 | year = 2003 | pmid = 12493763 | doi = 10.1074/jbc.M208992200 | doi-access = free }}</ref><ref name = pmid9804427>{{cite journal |vauthors=Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL | title = Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex | journal = Nature | volume = 395 | issue = 6705 | pages = 917–21 | year = 1998 | pmid = 9804427 | doi = 10.1038/27699 | bibcode = 1998Natur.395..917T | s2cid = 4355885 }}</ref> * HDAC3,<ref name = pmid11470869/> * MTA2,<ref name = pmid12920132/><ref name = pmid10444591/> * RB,<ref name = pmid11470869/><ref name = pmid7503932>{{cite journal |author2-link=Eva Y.-H. P. Lee |vauthors=Qian YW, Lee EY | title = Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast | journal = J. Biol. Chem. | volume = 270 | issue = 43 | pages = 25507–13 | year = 1995 | pmid = 7503932 | doi = 10.1074/jbc.270.43.25507| doi-access = free }}</ref><ref name = pmid10734134>{{cite journal |vauthors=Nicolas E, Morales V, Magnaghi-Jaulin L, Harel-Bellan A, Richard-Foy H, Trouche D | title = RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein | journal = J. Biol. Chem. | volume = 275 | issue = 13 | pages = 9797–804 | year = 2000 | pmid = 10734134 | doi = 10.1074/jbc.275.13.9797| doi-access = free }}</ref> * SAP30,<ref name = pmid10444591/><ref name = pmid9651585/><ref name = pmid11784859>{{cite journal |vauthors=Kuzmichev A, Zhang Y, Erdjument-Bromage H, Tempst P, Reinberg D | title = Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1) | journal = Mol. Cell. Biol. | volume = 22 | issue = 3 | pages = 835–48 | year = 2002 | pmid = 11784859 | pmc = 133546 | doi = 10.1128/MCB.22.3.835-848.2002}}</ref> and * SIN3A.<ref name = pmid9150133/><ref name = pmid9651585>{{cite journal |vauthors=Zhang Y, Sun ZW, Iratni R, Erdjument-Bromage H, Tempst P, Hampsey M, Reinberg D | title = SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex | journal = Mol. Cell | volume = 1 | issue = 7 | pages = 1021–31 | year = 1998 | pmid = 9651585 | doi = 10.1016/S1097-2765(00)80102-1| doi-access = free }}</ref> {{Clear}}
==References== {{Reflist|35em}}
==Further reading== {{Refbegin|35em}} * {{Cite web|title=RBBP4 retinoblastoma binding protein 4 [Homo sapiens (human)] |url=https://www.ncbi.nlm.nih.gov/gene/5928|publisher=National Center for Biotechnology Information (NCBI)|access-date=2013-09-06|location=Bethesda, MD}} * {{cite journal |author=Bauw G |title=Two-dimensional gel electrophoresis, protein electroblotting and microsequencing: a direct link between proteins and genes |journal=Electrophoresis |volume=11 |issue= 7 |pages= 528–36 |year= 1990 |pmid= 1699755 |doi= 10.1002/elps.1150110703 |author2=Rasmussen HH |author3=van den Bulcke M |last4=Damme |first4=Jozef Van |last5=Puype |first5=Magda |last6=Gesser |first6=Borbala |last7=Celis |first7=Julio E. |last8=Vandekerckhove |first8=Joël|s2cid=24768114 }} * {{cite journal |vauthors=Grozinger CM, Hassig CA, Schreiber SL |title=Three proteins define a class of human histone deacetylases related to yeast Hda1p |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 9 |pages= 4868–73 |year= 1999 |pmid= 10220385 |doi=10.1073/pnas.96.9.4868 |pmc=21783|bibcode=1999PNAS...96.4868G |doi-access=free }} * {{cite journal |author=Hassig CA |title=A role for histone deacetylase activity in HDAC1-mediated transcriptional repression |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 7 |pages= 3519–24 |year= 1998 |pmid= 9520398 |doi=10.1073/pnas.95.7.3519 |pmc=19868 |author2=Tong JK |author3=Fleischer TC |last4=Owa |first4=T |last5=Grable |first5=PG |last6=Ayer |first6=DE |last7=Schreiber |first7=SL|bibcode=1998PNAS...95.3519H |doi-access=free }} * {{cite journal |author=Marheineke K |author2=Krude T |title=Nucleosome assembly activity and intracellular localization of human CAF-1 changes during the cell division cycle |journal=J. Biol. Chem. |volume=273 |issue= 24 |pages= 15279–86 |year= 1998 |pmid= 9614144 |doi=10.1074/jbc.273.24.15279|doi-access=free }} * {{cite journal |author=Maruyama K |author2=Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8}} * {{cite journal |author=Qian YW |author2=Lee EY |title=Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast |journal=J. Biol. Chem. |volume=270 |issue= 43 |pages= 25507–13 |year= 1995 |pmid= 7503932 |doi=10.1074/jbc.270.43.25507|doi-access=free }} * {{cite journal |author=Rasmussen HH |title=Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes |journal=Electrophoresis |volume=13 |issue= 12 |pages= 960–9 |year= 1993 |pmid= 1286667 |doi=10.1002/elps.11501301199 |author2=van Damme J |author3=Puype M |last4=Gesser |first4=Borbala |last5=Celis |first5=Julio E. |last6=Vandekerckhove |first6=Joël|s2cid=41855774 }} * {{cite journal |author=Suzuki Y |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 |author2=Yoshitomo-Nakagawa K |author3=Maruyama K |last4=Suyama |first4=Akira |last5=Sugano |first5=Sumio}} * {{cite journal |vauthors=Taunton J, Hassig CA, Schreiber SL |title=A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p |journal=Science |volume=272 |issue= 5260 |pages= 408–11 |year= 1996 |pmid= 8602529 |doi=10.1126/science.272.5260.408|bibcode=1996Sci...272..408T |s2cid=25717734 }} * {{cite journal |author=Tong JK |title=Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex |journal=Nature |volume=395 |issue= 6705 |pages= 917–21 |year= 1998 |pmid= 9804427 |doi= 10.1038/27699 |author2=Hassig CA |author3=Schnitzler GR |last4=Schnitzler |first4=Gavin R. |last5=Kingston |first5=Robert E.|bibcode=1998Natur.395..917T |s2cid=4355885 }} * {{cite journal |author=Verreault A |author2=Kaufman PD |author3=Kobayashi R, Stillman B |title=Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase |journal=Curr. Biol. |volume=8 |issue= 2 |pages= 96–108 |year= 1998 |pmid= 9427644 |doi=10.1016/S0960-9822(98)70040-5|s2cid=201273 |doi-access=free |bibcode=1998CBio....8...96V }} * {{cite journal |author=Verreault A |author2=Kaufman PD |author3=Kobayashi R, Stillman B |title=Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4 |journal=Cell |volume=87 |issue= 1 |pages= 95–104 |year= 1996 |pmid= 8858152 |doi=10.1016/S0092-8674(00)81326-4|s2cid=1416453 |doi-access=free }} * {{cite journal |author=Wolffe AP |author2=Urnov FD |author3=Guschin D |title=Co-repressor complexes and remodelling chromatin for repression |journal=Biochem. Soc. Trans. |volume=28 |issue= 4 |pages= 379–86 |year= 2001 |pmid= 10961924 |doi=10.1042/0300-5127:0280379}} * {{cite journal |author=Yarden RI |author2=Brody LC |title=BRCA1 interacts with components of the histone deacetylase complex |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 9 |pages= 4983–8 |year= 1999 |pmid= 10220405 |doi=10.1073/pnas.96.9.4983 |pmc=21803|bibcode=1999PNAS...96.4983Y |doi-access=free }} * {{cite journal |author=Zhang Y |title=Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation |journal=Genes Dev. |volume=13 |issue= 15 |pages= 1924–35 |year= 1999 |pmid= 10444591 |doi=10.1101/gad.13.15.1924 |pmc=316920 |author2=Ng HH |author3=Erdjument-Bromage H |last4=Tempst |first4=P. |last5=Bird |first5=A. |last6=Reinberg |first6=D.}} * {{cite journal |author=Zhang Y |title=Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex |journal=Cell |volume=89 |issue= 3 |pages= 357–64 |year= 1997 |pmid= 9150135 |doi=10.1016/S0092-8674(00)80216-0 |author2=Iratni R |author3=Erdjument-Bromage H |last4=Tempst |first4=Paul |last5=Reinberg |first5=Danny|doi-access=free }} * {{cite journal |author=Zhang Y |title=SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex |journal=Mol. Cell |volume=1 |issue= 7 |pages= 1021–31 |year= 1998 |pmid= 9651585 |doi=10.1016/S1097-2765(00)80102-1 |author2=Sun ZW |author3=Iratni R |last4=Erdjument-Bromage |first4=Hediye |last5=Tempst |first5=Paul |last6=Hampsey |first6=Michael |last7=Reinberg |first7=Danny|doi-access=free }} * {{cite journal |author=Zhang Y |title=The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities |journal=Cell |volume=95 |issue= 2 |pages= 279–89 |year= 1998 |pmid= 9790534 |doi=10.1016/S0092-8674(00)81758-4 |author2=LeRoy G |author3=Seelig HP |last4=Lane |first4=William S |last5=Reinberg |first5=Danny|s2cid=18786866 |doi-access=free }} * {{cite journal |author=Zhang Y |author2=Dufau ML |title=Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes |journal=J. Steroid Biochem. Mol. Biol. |volume=85 |issue= 2–5 |pages= 401–14 |year= 2003 |pmid= 12943729 |doi=10.1016/S0960-0760(03)00230-9|s2cid=28512341 |url=https://zenodo.org/record/1260176}}
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