RBBP4
出典: フリー百科事典『ウィキペディア（Wikipedia）』 (2024/11/30 15:05 UTC 版)
RBBP4（retinoblastoma binding protein 4）は、ヒトではRBBP4遺伝子によってコードされるタンパク質である[5][6]。RbAp48（retinoblastoma-associated protein 48）、NURF55（nucleosome remodeling factor 55）といった名称でも知られる。
機能
RBBP4はWDリピートタンパク質ファミリーに属し、普遍的に発現している核内タンパク質であり、ヒストンのアセチル化やクロマチンの組み立てに関与するタンパク質複合体中に存在する。RBBP4はMi-2/NuRD複合体の一部を構成しており、この複合体はクロマチンリモデリングやヒストンの脱アセチル化と関連した転写抑制への関与が示唆されている。またこのタンパク質は、転写サイレンシングの重要な要素であるコリプレッサー複合体の一部にもなっている。Rbタンパク質と直接相互作用して細胞増殖を調節するタンパク質の1つであることも知られており、E2F応答性遺伝子の転写抑制にも関与しているようである[7]。
臨床的意義
脳内の海馬の歯状回におけるRBBP4の減少は、正常な老化過程における記憶の低下の主要因である可能性がある[8]。ヒトの剖検組織、そしてマウスでも、歯状回において加齢と関連したRBBP4の減少が観察される。さらに、ドミナントネガティブ型遺伝子のノックインによって、若齢マウスでも老齢マウスで観察されるような記憶の欠陥が引き起こされる。レンチウイルスを用いた遺伝子導入によって脳内でのRBBP4の発現を高めることで、老齢マウスの記憶の欠陥は回復する[8]。
RBBP4の作用の少なくとも一部は、PKA-CREB1-CBP経路を介したものである[8]。したがって、この経路を刺激する薬剤は、加齢と関連した記憶の低下を回復するための治療アプローチの1つとなる可能性がある。アデニル酸シクラーゼと正に共役しているD1/D5ドーパミン受容体に対するアゴニストである6-Br-APBやSKF-38,393、cAMPホスホジエステラーゼ阻害薬であるロリプラムは老齢マウスの記憶の欠陥を低減することが示されている[9]。
相互作用
RBBP4は次に挙げる因子と荘祖作用することが示されている。
- BRCA1[10]
- CRREBBP[11]
- GATAD2B,[12]
- HDAC1[13][14][15][16][17][18][19][20][21][22][23]
- HDAC2[13][21][24][25]
- HDAC3[15]
- MTA2[14][20]
- RB[15][26][27]
- SAP30[20][28][29]
- SIN3A[18][28]
出典
- ^ a b c GRCh38: Ensembl release 89: ENSG00000162521 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000057236 - Ensembl, May 2017
- ^ Human PubMed Reference:
- ^ Mouse PubMed Reference:
- ^ “A retinoblastoma-binding protein related to a negative regulator of Ras in yeast”. Nature 364 (6438): 648–52. (September 1993). Bibcode: 1993Natur.364..648Q. doi:10.1038/364648a0. PMID 8350924.
- ^ “Isolation of human NURF: a regulator of Engrailed gene expression”. EMBO J 22 (22): 6089–100. (November 2003). doi:10.1093/emboj/cdg582. PMC 275440. PMID 14609955.
- ^ “Entrez Gene: RBBP4 retinoblastoma-binding protein 4”. 2024年11月30日閲覧。
- ^ a b c “Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48”. Sci Transl Med 5 (200): 200ra115. (August 2013). doi:10.1126/scitranslmed.3006373. PMC 4940031. PMID 23986399.
- ^ “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”. Proc. Natl. Acad. Sci. U.S.A. 96 (9): 5280–5. (April 1999). Bibcode: 1999PNAS...96.5280B. doi:10.1073/pnas.96.9.5280. PMC 21855. PMID 10220457.
- ^ “BRCA1 interacts with components of the histone deacetylase complex”. Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4983–8. (1999). Bibcode: 1999PNAS...96.4983Y. doi:10.1073/pnas.96.9.4983. PMC 21803. PMID 10220405.
- ^ “Histone binding protein RbAp48 interacts with a complex of CREB binding protein and phosphorylated CREB”. Mol. Cell. Biol. 20 (14): 4970–8. (2000). doi:10.1128/MCB.20.14.4970-4978.2000. PMC 85947. PMID 10866654.
- ^ “Identification and functional characterization of the p66/p68 components of the MeCP1 complex”. Mol. Cell. Biol. 22 (2): 536–46. (2002). doi:10.1128/MCB.22.2.536-546.2002. PMC 139742. PMID 11756549.
- ^ a b “Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes”. J. Steroid Biochem. Mol. Biol. 85 (2–5): 401–14. (2003). doi:10.1016/S0960-0760(03)00230-9. PMID 12943729.
- ^ a b “The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity”. J. Biol. Chem. 278 (43): 42560–8. (2003). doi:10.1074/jbc.M302955200. PMID 12920132.
- ^ a b c “The histone deacetylase HDAC3 targets RbAp48 to the retinoblastoma protein”. Nucleic Acids Res. 29 (15): 3131–6. (2001). doi:10.1093/nar/29.15.3131. PMC 55834. PMID 11470869.
- ^ “Three proteins define a class of human histone deacetylases related to yeast Hda1p”. Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4868–73. (1999). Bibcode: 1999PNAS...96.4868G. doi:10.1073/pnas.96.9.4868. PMC 21783. PMID 10220385.
- ^ “CoREST is an integral component of the CoREST- human histone deacetylase complex”. Proc. Natl. Acad. Sci. U.S.A. 98 (4): 1454–8. (2001). Bibcode: 2001PNAS...98.1454Y. doi:10.1073/pnas.98.4.1454. PMC 29278. PMID 11171972.
- ^ a b “Histone deacetylase activity is required for full transcriptional repression by mSin3A”. Cell 89 (3): 341–7. (1997). doi:10.1016/S0092-8674(00)80214-7. PMID 9150133.
- ^ “MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex”. Nat. Genet. 23 (1): 58–61. (1999). doi:10.1038/12659. hdl:1842/684. PMID 10471499.
- ^ a b c “Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation”. Genes Dev. 13 (15): 1924–35. (1999). doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591.
- ^ a b “Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex”. J. Biol. Chem. 277 (36): 33431–8. (2002). doi:10.1074/jbc.M204417200. PMID 12091390.
- ^ “A role for histone deacetylase activity in HDAC1-mediated transcriptional repression”. Proc. Natl. Acad. Sci. U.S.A. 95 (7): 3519–24. (1998). Bibcode: 1998PNAS...95.3519H. doi:10.1073/pnas.95.7.3519. PMC 19868. PMID 9520398.
- ^ “Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex”. Cell 89 (3): 357–64. (1997). doi:10.1016/S0092-8674(00)80216-0. PMID 9150135.
- ^ “A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes”. J. Biol. Chem. 278 (9): 7234–9. (2003). doi:10.1074/jbc.M208992200. PMID 12493763.
- ^ “Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex”. Nature 395 (6705): 917–21. (1998). Bibcode: 1998Natur.395..917T. doi:10.1038/27699. PMID 9804427.
- ^ “Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast”. J. Biol. Chem. 270 (43): 25507–13. (1995). doi:10.1074/jbc.270.43.25507. PMID 7503932.
- ^ “RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein”. J. Biol. Chem. 275 (13): 9797–804. (2000). doi:10.1074/jbc.275.13.9797. PMID 10734134.
- ^ a b “SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex”. Mol. Cell 1 (7): 1021–31. (1998). doi:10.1016/S1097-2765(00)80102-1. PMID 9651585.
- ^ “Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1)”. Mol. Cell. Biol. 22 (3): 835–48. (2002). doi:10.1128/MCB.22.3.835-848.2002. PMC 133546. PMID 11784859.
関連文献
- “RBBP4 retinoblastoma binding protein 4 [Homo sapiens (human)]”. Home - Gene - NCBI. Bethesda, MD: National Center for Biotechnology Information (NCBI). 2013年9月6日閲覧。
- Bauw G; Rasmussen HH; van den Bulcke M; Damme, Jozef Van; Puype, Magda; Gesser, Borbala; Celis, Julio E.; Vandekerckhove, Joël (1990). “Two-dimensional gel electrophoresis, protein electroblotting and microsequencing: a direct link between proteins and genes”. Electrophoresis 11 (7): 528–36. doi:10.1002/elps.1150110703. PMID 1699755.
- “Three proteins define a class of human histone deacetylases related to yeast Hda1p”. Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4868–73. (1999). Bibcode: 1999PNAS...96.4868G. doi:10.1073/pnas.96.9.4868. PMC 21783. PMID 10220385.
- Hassig CA; Tong JK; Fleischer TC; Owa, T; Grable, PG; Ayer, DE; Schreiber, SL (1998). “A role for histone deacetylase activity in HDAC1-mediated transcriptional repression”. Proc. Natl. Acad. Sci. U.S.A. 95 (7): 3519–24. Bibcode: 1998PNAS...95.3519H. doi:10.1073/pnas.95.7.3519. PMC 19868. PMID 9520398.
- Marheineke K; Krude T (1998). “Nucleosome assembly activity and intracellular localization of human CAF-1 changes during the cell division cycle”. J. Biol. Chem. 273 (24): 15279–86. doi:10.1074/jbc.273.24.15279. PMID 9614144.
- Maruyama K; Sugano S (1994). “Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides”. Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Qian YW; Lee EY (1995). “Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast”. J. Biol. Chem. 270 (43): 25507–13. doi:10.1074/jbc.270.43.25507. PMID 7503932.
- Rasmussen HH; van Damme J; Puype M; Gesser, Borbala; Celis, Julio E.; Vandekerckhove, Joël (1993). “Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes”. Electrophoresis 13 (12): 960–9. doi:10.1002/elps.11501301199. PMID 1286667.
- Suzuki Y; Yoshitomo-Nakagawa K; Maruyama K; Suyama, Akira; Sugano, Sumio (1997). “Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library”. Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- “A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p”. Science 272 (5260): 408–11. (1996). Bibcode: 1996Sci...272..408T. doi:10.1126/science.272.5260.408. PMID 8602529.
- Tong JK; Hassig CA; Schnitzler GR; Schnitzler, Gavin R.; Kingston, Robert E. (1998). “Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex”. Nature 395 (6705): 917–21. Bibcode: 1998Natur.395..917T. doi:10.1038/27699. PMID 9804427.
- Verreault A; Kaufman PD; Kobayashi R, Stillman B (1998). “Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase”. Curr. Biol. 8 (2): 96–108. Bibcode: 1998CBio....8...96V. doi:10.1016/S0960-9822(98)70040-5. PMID 9427644.
- Verreault A; Kaufman PD; Kobayashi R, Stillman B (1996). “Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4”. Cell 87 (1): 95–104. doi:10.1016/S0092-8674(00)81326-4. PMID 8858152.
- Wolffe AP; Urnov FD; Guschin D (2001). “Co-repressor complexes and remodelling chromatin for repression”. Biochem. Soc. Trans. 28 (4): 379–86. doi:10.1042/0300-5127:0280379. PMID 10961924.
- Yarden RI; Brody LC (1999). “BRCA1 interacts with components of the histone deacetylase complex”. Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4983–8. Bibcode: 1999PNAS...96.4983Y. doi:10.1073/pnas.96.9.4983. PMC 21803. PMID 10220405.
- Zhang Y; Ng HH; Erdjument-Bromage H; Tempst, P.; Bird, A.; Reinberg, D. (1999). “Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation”. Genes Dev. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591.
- Zhang Y; Iratni R; Erdjument-Bromage H; Tempst, Paul; Reinberg, Danny (1997). “Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex”. Cell 89 (3): 357–64. doi:10.1016/S0092-8674(00)80216-0. PMID 9150135.
- Zhang Y; Sun ZW; Iratni R; Erdjument-Bromage, Hediye; Tempst, Paul; Hampsey, Michael; Reinberg, Danny (1998). “SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex”. Mol. Cell 1 (7): 1021–31. doi:10.1016/S1097-2765(00)80102-1. PMID 9651585.
- Zhang Y; LeRoy G; Seelig HP; Lane, William S; Reinberg, Danny (1998). “The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities”. Cell 95 (2): 279–89. doi:10.1016/S0092-8674(00)81758-4. PMID 9790534.
- Zhang Y; Dufau ML (2003). “Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes”. J. Steroid Biochem. Mol. Biol. 85 (2–5): 401–14. doi:10.1016/S0960-0760(03)00230-9. PMID 12943729.
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