RBBP8

RBBP8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2L4Z, 4D2H
Identifiers
Aliases	RBBP8 , COM1, CTIP, JWDS, RIM, SAE2, SCKL2, retinoblastoma binding protein 8, RB binding protein 8, endonuclease
External IDs	OMIM: 604124; MGI: 2442995; HomoloGene: 28546; GeneCards: RBBP8; OMA:RBBP8 - orthologs
Gene location (Human) Chr. Chromosome 18 (human) [1] Band 18q11.2 Start 22,798,261 bp [1] End 23,026,488 bp [1]
Gene location (Mouse) Chr. Chromosome 18 (mouse) [2] Band 18|18 A1 Start 11,766,333 bp [2] End 11,878,278 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Epithelium of choroid plexus gonad testicle kidney tubule caput epididymis epithelium of lactiferous gland skin of hip lactiferous duct ventricular zone islet of Langerhans Top expressed in genital tubercle tail of embryo vestibular sensory epithelium zygote urothelium medullary collecting duct primitive streak spermatocyte secondary oocyte transitional epithelium of urinary bladder More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nuclease activity hydrolase activity endonuclease activity transcription corepressor activity damaged DNA binding DNA binding protein binding single-stranded DNA endodeoxyribonuclease activity identical protein binding Y-form DNA binding double-strand/single-strand DNA junction binding double-stranded DNA binding single-stranded DNA binding flap-structured DNA binding Cellular component transcription repressor complex chromosome nucleus nucleoplasm intracellular membrane-bounded organelle site of double-strand break Biological process cell cycle DNA repair nucleotide-excision repair cell division nucleic acid phosphodiester bond hydrolysis response to estradiol meiosis regulation of transcription by RNA polymerase II cellular response to DNA damage stimulus blastocyst hatching DNA double-strand break processing DNA replication DNA double-strand break processing involved in repair via single-strand annealing negative regulation of transcription by RNA polymerase II double-strand break repair via homologous recombination negative regulation of G0 to G1 transition negative regulation of nucleic acid-templated transcription G1/S transition of mitotic cell cycle regulation of signal transduction by p53 class mediator Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5932 225182 Ensembl ENSG00000101773 ENSMUSG00000041238 UniProt Q99708 Q80YR6 RefSeq (mRNA) NM_002894 NM_203291 NM_203292 NM_001081223 NM_001252495 NM_175458 RefSeq (protein) NP_002885 NP_976036 NP_976037 NP_002885.1 NP_976036.1 NP_001074692 NP_001239424 Location (UCSC) Chr 18: 22.8 – 23.03 Mb Chr 18: 11.77 – 11.88 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Retinoblastoma-binding protein 8 is a protein that in humans is encoded by the RBBP8 gene. ^{[5] [6] [7]}

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. ^[7]

DNA repair

RBBP8 is involved in the DNA repair process of homologous recombination. ^[8] It was proposed that, in gastric cancer cells, inhibition of RBBP8 expression could cause a synthetic lethal effect along with PARP inhibitor treatment. ^[8]

Interactions

RBBP8 has been shown to interact with:

• ATM, ^{[9] [10]}
• BRCA1, ^{[9] [11] [12] [13] [14] [15] [16]}
• CTBP1, ^{[11] [17]}
• LMO4, ^{[18] [19]}
• RB1, ^{[5] [20]}
• RBL1, ^{[5] [21]}
• RBL2, ^{[5] [22]} and
• SIAH1 ^[23]

References

1. GRCh38: Ensembl release 89: ENSG00000101773 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000041238 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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. Bibcode:2007Natur.450..509S. doi:10.1038/nature06337. PMC   2409435 . PMID   17965729.
7. "Entrez Gene: RBBP8 retinoblastoma binding protein 8".
8. Yu Y, Wang S, Yin Y, Wang G (September 2023). "Mechanism of RBBP8-mediated homologous recombination repair in gastric cancer synthetic lethal". Chronic Dis Transl Med. 9 (3): 250–257. doi:10.1002/cdt3.75. PMC   10497805 . PMID   37711862.
9. 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. S2CID   3266654.
10. 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.
11. 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.
12. 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.
13. 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. S2CID   23495632.
14. 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. S2CID   4329675.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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. S2CID   20908722.
20. 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.
21. 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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
22. 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. Bibcode:1999PNAS...96.9574M. doi: 10.1073/pnas.96.17.9574 . PMC   22250 . PMID   10449734.
23. 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. S2CID   28860630.
• 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. S2CID   23495632.
• 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. Bibcode:1999PNAS...96.9574M. 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. doi: 10.1096/fasebj.14.7.904 . PMID   10783144. S2CID   43175069.
• 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. S2CID   3266654.
• 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. S2CID   4329675.
• 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.