RBBP8

Retinoblastoma binding protein 8
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2L4Z​, 4D2H​
Identifiers
Symbols	RBBP8 ; COM1; CTIP; JWDS; RIM; SAE2; SCKL2
External IDs	OMIM: 604124 MGI: 2442995 HomoloGene: 28546 GeneCards: RBBP8 Gene
Gene ontology Molecular function • single-stranded DNA endodeoxyribonuclease activity • RNA polymerase II repressing transcription factor binding • RNA polymerase II transcription corepressor activity • damaged DNA binding • protein binding Cellular component • nucleus • nucleoplasm • nucleolus • transcriptional repressor complex Biological process • cell cycle checkpoint • G1/S transition of mitotic cell cycle • negative regulation of transcription from RNA polymerase II promoter • double-strand break repair via homologous recombination • blastocyst hatching • DNA repair • nucleotide-excision repair • regulation of transcription from RNA polymerase II promoter • mitotic nuclear division • DNA double-strand break processing involved in repair via single-strand annealing • G2 DNA damage checkpoint • response to estradiol • cell division • meiotic cell cycle • nucleic acid phosphodiester bond hydrolysis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5932	225182
Ensembl	ENSG00000101773	ENSMUSG00000041238
UniProt	Q99708	Q80YR6
RefSeq (mRNA)	NM_002894	NM_001081223
RefSeq (protein)	NP_002885	NP_001074692
Location (UCSC)	Chr 18: 22.8 – 23.03 Mb	Chr 18: 11.63 – 11.74 Mb
PubMed search

Retinoblastoma-binding protein 8 is a protein that in humans is encoded by the RBBP8 gene.^[1][2][3]

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][11]}
• CTBP1,^[6][12]
• LMO4,^[13][14]
• RB1,^[1][15]
• RBL1,^[1][16]
• RBL2,^[1]{^[17] and
• SIAH1^[18]

References

1. Fusco C, Reymond A, Zervos AS (October 1998). "Molecular cloning and characterization of a novel retinoblastoma-binding protein". Genomics 51 (3): 351–8. doi:10.1006/geno.1998.5368. PMID 9721205.
2. Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP (November 2007). "Human CtIP promotes DNA end resection". Nature 450 (7169): 509–14. doi:10.1038/nature06337. PMC 2409435. PMID 17965729.
3. "Entrez Gene: RBBP8 retinoblastoma binding protein 8".
4. Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY, Lee WH (July 2000). "Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response". Nature 406 (6792): 210–5. doi:10.1038/35018134. PMID 10910365.
5. Kim ST, Lim DS, Canman CE, Kastan MB (Dec 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID 10608806.
6. Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD, Lee WH (April 1999). "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. doi:10.1074/jbc.274.16.11334. PMID 10196224.
7. Rodriguez M, Yu X, Chen J, Songyang Z (Dec 2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. Biol. Chem. 278 (52): 52914–8. doi:10.1074/jbc.C300407200. PMID 14578343.
8. 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 (November 1998). "Characterization of a carboxy-terminal BRCA1 interacting protein". Oncogene 17 (18): 2279–85. doi:10.1038/sj.onc.1202150. PMID 9811458.
9. Wu-Baer F, Baer R (November 2001). "Effect of DNA damage on a BRCA1 complex". Nature 414 (6859): 36. doi:10.1038/35102118. PMID 11689934.
10. Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R (September 1998). "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. doi:10.1074/jbc.273.39.25388. PMID 9738006.
11. Yu X, Baer R (June 2000). "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. doi:10.1074/jbc.M909494199. PMID 10764811.
12. Schaeper U, Subramanian T, Lim L, Boyd JM, Chinnadurai G (April 1998). "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. doi:10.1074/jbc.273.15.8549. PMID 9535825.
13. Sum EY, Peng B, Yu X, Chen J, Byrne J, Lindeman GJ, Visvader JE (March 2002). "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. doi:10.1074/jbc.M110603200. PMID 11751867.
14. Sutherland KD, Visvader JE, Choong DY, Sum EY, Lindeman GJ, Campbell IG (October 2003). "Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas". Int. J. Cancer 107 (1): 155–8. doi:10.1002/ijc.11343. PMID 12925972.
15. Dick FA, Sailhamer E, Dyson NJ (May 2000). "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. doi:10.1128/mcb.20.10.3715-3727.2000. PMC 85672. PMID 10779361.
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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
17. Meloni AR, Smith EJ, Nevins JR (August 1999). "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. doi:10.1073/pnas.96.17.9574. PMC 22250. PMID 10449734.
18. Germani A, Prabel A, Mourah S, Podgorniak MP, Di Carlo A, Ehrlich R, Gisselbrecht S, Varin-Blank N, Calvo F, Bruzzoni-Giovanelli H (Dec 2003). "SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway". Oncogene 22 (55): 8845–51. doi:10.1038/sj.onc.1206994. PMID 14654780.

Further reading

• Deng CX, Brodie SG (2000). "Roles of BRCA1 and its interacting proteins". BioEssays 22 (8): 728–37. doi:10.1002/1521-1878(200008)22:8<728::AID-BIES6>3.0.CO;2-B. PMID 10918303.
• Matoba R, Okubo K, Hori N, Fukushima A, Matsubara K (1994). "The addition of 5'-coding information to a 3'-directed cDNA library improves analysis of gene expression". Gene 146 (2): 199–207. doi:10.1016/0378-1119(94)90293-3. PMID 8076819.
• Schaeper U, Subramanian T, Lim L, Boyd JM, Chinnadurai G (1998). "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. doi:10.1074/jbc.273.15.8549. PMID 9535825.
• Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R (1998). "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. doi:10.1074/jbc.273.39.25388. PMID 9738006.
• 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 (1998). "Characterization of a carboxy-terminal BRCA1 interacting protein". Oncogene 17 (18): 2279–85. doi:10.1038/sj.onc.1202150. PMID 9811458.
• Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD, Lee WH (1999). "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. doi:10.1074/jbc.274.16.11334. PMID 10196224.
• Meloni AR, Smith EJ, Nevins JR (1999). "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. doi:10.1073/pnas.96.17.9574. PMC 22250. PMID 10449734.
• Kim ST, Lim DS, Canman CE, Kastan MB (2000). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID 10608806.
• Yu X, Baer R (2000). "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. doi:10.1074/jbc.M909494199. PMID 10764811.
• Dick FA, Sailhamer E, Dyson NJ (2000). "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. doi:10.1128/MCB.20.10.3715-3727.2000. PMC 85672. PMID 10779361.
• Fanciulli M, Bruno T, Di Padova M, De Angelis R, Iezzi S, Iacobini C, Floridi A, Passananti C (2000). "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. PMID 10783144.
• Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY, Lee WH (2000). "Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response". Nature 406 (6792): 210–5. doi:10.1038/35018134. PMID 10910365.
• Zheng L, Pan H, Li S, Flesken-Nikitin A, Chen PL, Boyer TG, Lee WH (2000). "Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1". Mol. Cell 6 (4): 757–68. doi:10.1016/S1097-2765(00)00075-7. PMID 11090615.
• Izutsu K, Kurokawa M, Imai Y, Maki K, Mitani K, Hirai H (2001). "The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling". Blood 97 (9): 2815–22. doi:10.1182/blood.V97.9.2815. PMID 11313276.
• Melhuish TA, Gallo CM, Wotton D (2001). "TGIF2 interacts with histone deacetylase 1 and represses transcription". J. Biol. Chem. 276 (34): 32109–14. doi:10.1074/jbc.M103377200. PMID 11427533.
• Wu-Baer F, Baer R (2001). "Effect of DNA damage on a BRCA1 complex". Nature 414 (6859): 36. doi:10.1038/35102118. PMID 11689934.
• Sum EY, Peng B, Yu X, Chen J, Byrne J, Lindeman GJ, Visvader JE (2002). "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. doi:10.1074/jbc.M110603200. PMID 11751867.
• Koipally J, Georgopoulos K (2002). "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. doi:10.1074/jbc.M202079200. PMID 11959865.