RBBP8 explained

Retinoblastoma-binding protein 8 is a protein that in humans is encoded by the RBBP8 gene.^{[1] [2]}

Function

The protein encoded by this gene is a ubiquitously expressed nuclear protein. It is found among several proteins that bind directly to retinoblastoma protein, which regulates cell proliferation. This protein complexes with transcriptional co-repressor CTBP. It is also associated with BRCA1 and is thought to modulate the functions of BRCA1 in transcriptional regulation, DNA repair, and/or cell cycle checkpoint control. It is suggested that this gene may itself be a tumor suppressor acting in the same pathway as BRCA1. Three transcript variants encoding two different isoforms have been found for this gene. More transcript variants exist, but their full-length natures have not been determined.^[3]

Interactions

RBBP8 has been shown to interact with:

• ATM,^{[4] [5]}
• BRCA1,^{[4] [6] [7] [8] [9] [10]}
• CTBP1,^{[11] [12]}
• LMO4,^{[13] [14]}
• RB1,^{[1] [15]}
• RBL1,^{[1] [16]}
• RBL2,^[17] and
• SIAH1^[18]

Further reading

• Deng CX, Brodie SG . Roles of BRCA1 and its interacting proteins . BioEssays . 22 . 8 . 728–37 . 2000 . 10918303 . 10.1002/1521-1878(200008)22:8<728::AID-BIES6>3.0.CO;2-B . 28860630 .
• Matoba R, Okubo K, Hori N, Fukushima A, Matsubara K . The addition of 5'-coding information to a 3'-directed cDNA library improves analysis of gene expression . Gene . 146 . 2 . 199–207 . 1994 . 8076819 . 10.1016/0378-1119(94)90293-3 .
• Schaeper U, Subramanian T, Lim L, Boyd JM, Chinnadurai G . Interaction between a cellular protein that binds to the C-terminal region of adenovirus E1A (CtBP) and a novel cellular protein is disrupted by E1A through a conserved PLDLS motif . J. Biol. Chem. . 273 . 15 . 8549–52 . 1998 . 9535825 . 10.1074/jbc.273.15.8549 . free .
• Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R . The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression . J. Biol. Chem. . 273 . 39 . 25388–92 . 1998 . 9738006 . 10.1074/jbc.273.39.25388 . free .
• Wong AK, Ormonde PA, Pero R, Chen Y, Lian L, Salada G, Berry S, Lawrence Q, Dayananth P, Ha P, Tavtigian SV, Teng DH, Bartel PL . Characterization of a carboxy-terminal BRCA1 interacting protein . Oncogene . 17 . 18 . 2279–85 . 1998 . 9811458 . 10.1038/sj.onc.1202150 . 23495632 .
• Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD, Lee WH . Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage . J. Biol. Chem. . 274 . 16 . 11334–8 . 1999 . 10196224 . 10.1074/jbc.274.16.11334 . free .
• Meloni AR, Smith EJ, Nevins JR . A mechanism for Rb/p130-mediated transcription repression involving recruitment of the CtBP corepressor . Proc. Natl. Acad. Sci. U.S.A. . 96 . 17 . 9574–9 . 1999 . 10449734 . 22250 . 10.1073/pnas.96.17.9574 . 1999PNAS...96.9574M . free .
• Kim ST, Lim DS, Canman CE, Kastan MB . Substrate specificities and identification of putative substrates of ATM kinase family members . J. Biol. Chem. . 274 . 53 . 37538–43 . 2000 . 10608806 . 10.1074/jbc.274.53.37538 . free .
• Yu X, Baer R . Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor . J. Biol. Chem. . 275 . 24 . 18541–9 . 2000 . 10764811 . 10.1074/jbc.M909494199 . free .
• Dick FA, Sailhamer E, Dyson NJ . Mutagenesis of the pRB Pocket Reveals that Cell Cycle Arrest Functions Are Separable from Binding to Viral Oncoproteins . Mol. Cell. Biol. . 20 . 10 . 3715–27 . 2000 . 10779361 . 85672 . 10.1128/MCB.20.10.3715-3727.2000 .
• Fanciulli M, Bruno T, Di Padova M, De Angelis R, Iezzi S, Iacobini C, Floridi A, Passananti C . Identification of a novel partner of RNA polymerase II subunit 11, Che-1, which interacts with and affects the growth suppression function of Rb . FASEB J. . 14 . 7 . 904–12 . 2000 . 10783144 . 10.1096/fasebj.14.7.904. free . 43175069 .
• Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY, Lee WH . Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response . Nature . 406 . 6792 . 210–5 . 2000 . 10910365 . 10.1038/35018134 . 3266654 .
• Zheng L, Pan H, Li S, Flesken-Nikitin A, Chen PL, Boyer TG, Lee WH . Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1 . Mol. Cell . 6 . 4 . 757–68 . 2000 . 11090615 . 10.1016/S1097-2765(00)00075-7 . free .
• Izutsu K, Kurokawa M, Imai Y, Maki K, Mitani K, Hirai H . The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling . Blood . 97 . 9 . 2815–22 . 2001 . 11313276 . 10.1182/blood.V97.9.2815 . free .
• Melhuish TA, Gallo CM, Wotton D . TGIF2 interacts with histone deacetylase 1 and represses transcription . J. Biol. Chem. . 276 . 34 . 32109–14 . 2001 . 11427533 . 10.1074/jbc.M103377200 . free .
• Wu-Baer F, Baer R . Effect of DNA damage on a BRCA1 complex . Nature . 414 . 6859 . 36 . 2001 . 11689934 . 10.1038/35102118 . 4329675 . free .
• Sum EY, Peng B, Yu X, Chen J, Byrne J, Lindeman GJ, Visvader JE . The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity . J. Biol. Chem. . 277 . 10 . 7849–56 . 2002 . 11751867 . 10.1074/jbc.M110603200 . free .
• Koipally J, Georgopoulos K . Ikaros-CtIP interactions do not require C-terminal binding protein and participate in a deacetylase-independent mode of repression . J. Biol. Chem. . 277 . 26 . 23143–9 . 2002 . 11959865 . 10.1074/jbc.M202079200 . free .

Notes and References

1. Fusco C, Reymond A, Zervos AS . Molecular cloning and characterization of a novel retinoblastoma-binding protein . Genomics . 51 . 3 . 351–8 . October 1998 . 9721205 . 10.1006/geno.1998.5368 .
2. Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP . Human CtIP promotes DNA end resection . Nature . 450 . 7169 . 509–14 . November 2007 . 17965729 . 2409435 . 10.1038/nature06337 . 2007Natur.450..509S .
3. Web site: Entrez Gene: RBBP8 retinoblastoma binding protein 8.
4. Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY, Lee WH . Eva Y.-H. P. Lee . Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response . Nature . 406 . 6792 . 210–5 . July 2000 . 10910365 . 10.1038/35018134 . 3266654 .
5. Kim ST, Lim DS, Canman CE, Kastan MB . Substrate specificities and identification of putative substrates of ATM kinase family members . J. Biol. Chem. . 274 . 53 . 37538–43 . Dec 1999 . 10608806 . 10.1074/jbc.274.53.37538. free .
6. Rodriguez M, Yu X, Chen J, Songyang Z . Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains . J. Biol. Chem. . 278 . 52 . 52914–8 . Dec 2003 . 14578343 . 10.1074/jbc.C300407200 . free .
7. Wong AK, Ormonde PA, Pero R, Chen Y, Lian L, Salada G, Berry S, Lawrence Q, Dayananth P, Ha P, Tavtigian SV, Teng DH, Bartel PL . Characterization of a carboxy-terminal BRCA1 interacting protein . Oncogene . 17 . 18 . 2279–85 . November 1998 . 9811458 . 10.1038/sj.onc.1202150 . 23495632 .
8. Wu-Baer F, Baer R . Effect of DNA damage on a BRCA1 complex . Nature . 414 . 6859 . 36 . November 2001 . 11689934 . 10.1038/35102118 . 4329675 . free .
9. Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R . The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression . J. Biol. Chem. . 273 . 39 . 25388–92 . September 1998 . 9738006 . 10.1074/jbc.273.39.25388. free .
10. Yu X, Baer R . Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor . J. Biol. Chem. . 275 . 24 . 18541–9 . June 2000 . 10764811 . 10.1074/jbc.M909494199 . free .
11. Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD, Lee WH . Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage . J. Biol. Chem. . 274 . 16 . 11334–8 . April 1999 . 10196224 . 10.1074/jbc.274.16.11334. free .
12. Schaeper U, Subramanian T, Lim L, Boyd JM, Chinnadurai G . Interaction between a cellular protein that binds to the C-terminal region of adenovirus E1A (CtBP) and a novel cellular protein is disrupted by E1A through a conserved PLDLS motif . J. Biol. Chem. . 273 . 15 . 8549–52 . April 1998 . 9535825 . 10.1074/jbc.273.15.8549. free .
13. Sum EY, Peng B, Yu X, Chen J, Byrne J, Lindeman GJ, Visvader JE . The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity . J. Biol. Chem. . 277 . 10 . 7849–56 . March 2002 . 11751867 . 10.1074/jbc.M110603200 . free .
14. Sutherland KD, Visvader JE, Choong DY, Sum EY, Lindeman GJ, Campbell IG . Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas . Int. J. Cancer . 107 . 1 . 155–8 . October 2003 . 12925972 . 10.1002/ijc.11343 . 20908722 . free .
15. Dick FA, Sailhamer E, Dyson NJ . Mutagenesis of the pRB pocket reveals that cell cycle arrest functions are separable from binding to viral oncoproteins . Mol. Cell. Biol. . 20 . 10 . 3715–27 . May 2000 . 10779361 . 85672 . 10.1128/mcb.20.10.3715-3727.2000.
16. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
17. Meloni AR, Smith EJ, Nevins JR . A mechanism for Rb/p130-mediated transcription repression involving recruitment of the CtBP corepressor . Proc. Natl. Acad. Sci. U.S.A. . 96 . 17 . 9574–9 . August 1999 . 10449734 . 22250 . 10.1073/pnas.96.17.9574. 1999PNAS...96.9574M . free .
18. Germani A, Prabel A, Mourah S, Podgorniak MP, Di Carlo A, Ehrlich R, Gisselbrecht S, Varin-Blank N, Calvo F, Bruzzoni-Giovanelli H . SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway . Oncogene . 22 . 55 . 8845–51 . Dec 2003 . 14654780 . 10.1038/sj.onc.1206994 . free .