retinoblastoma-associated protein (pRb, Rb, pp110, p105-Rb, p110Rb, RB1)
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Function
- may associate with the DNA replication complex
- regulates entry into cell division
- tumor suppressor
- transcription repressor of E2F1 target genes
- underphosphorylated, active form of RB1 interacts with E2F1 & represses its transcription activity, leading to cell cycle arrest
- directly involved in heterochromatin formation by maintaining overall chromatin structure, epspecilly constitutive heterochromatin by stabilizing histone methylation
- recruits & targets histone methyltransferases SUV39H1, SUV420H1 & SUV420H2, leading to epigenetic transcriptional repression
- controls histone H4 Lys-20 trimethylation
- inhibits the intrinsic kinase activity of TAF1
- in case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thus disrupting RB1's activity
- binds to UBF1 via one of the UBF1 HMG boxes thus inhibiting transcription of rDNA by RNA polymerase-1 (4b).
- since UBF1 is required for transcription from TATA-containing promoters, binding to UBF1 may also generally affect RNA-polymerase 2 transcription of TATA box-containing genes
- RB1 can repress transcription by RNA polymerase 3[6]
- interacts with ATAD5 (putative)
- hypophosphorylated form interacts with & sequesters E2F1
- unphosphorylated form interacts with ARID3B, JARID1A, SUV39H1, MJD2A/JHDM3A & THOC1
- interacts with N-terminal domain of TAF1
- interacts with AATF, DNMT1, LIN9, LMNA, SUV420H1, SUV420H2, PELP1 & TMPO-alpha
- may interact with NDC80
- interacts with EID1 & UBR4
- interacts with ARID4A & JARID1B
- interacts with E4F1
- interacts with adenovirus E1A protein, HPV E7 protein & SV40 large T antigen
- phosphorylated in G1, thereby releasing E2F1 which is then able to activate cell growth
- dephosphorylated at the late M phase
- SV40 large T antigen, HPV E7 & adenovirus E1A bind to the underphosphorylated, active form of pRb
Structure
belongs to the retinoblastoma protein (RB) family
Compartment
Expression
expressed in the retina
Pathology
- defects in RB1 are the cause of childhood cancer retinoblastoma
- defects in RB1 are a cause of
Laboratory
- Retinoblastoma protein in tissue (by Immune stain)
Comparative biology
- mice homozygous for an Rb mutation die in utero (E13.5-15.5) with defects in fetal hematopoiesis & widespread neuronal death[5].
- animals heterozygous for defective Rb protein are viable, but develop a variety of tumors
- the most common neoplasms in Rb heterozygous mice are intermediate lobe pituitary tumors & medullary thyroid carcinomas
- Rb & p53 mutations interact; mutant mice heterozygous for both p53 & Rb mutation have reduced viability & exhibit novel pathology including retinal dysplasia & increased tumor load & metastatic spread
More general terms
Additional terms
- Rb-related protein p130; retinoblastoma-like protein 2; RBR-2; PRB2; 130 kD retinoblastoma-associated protein; p130 (RBL2 RB2)
- retinoblastoma binding protein 1; AT-rich interactive domain-containing protein 4A; ARID domain-containing protein 4A; RBBP-1 (ARID4A, RBBP1, RBP1)
- retinoblastoma binding protein 2; histone demethylase JARID1A; Jumonji/ARID domain-containing protein 1A; RBBP-2 (JARID1A, RBBP2, RBP2, KDM5A)
- retinoblastoma-associated protein-like p107 homolog; retinoblastoma-like protein 1; PRB1; 107 kD retinoblastoma-associated protein; p107 (RBL1)
References
- ↑ Seizinger & Breakefield TINS 13(1) 3 (1990)
- ↑ Wilcock D, Lane DP. Localization of p53, retinoblastoma and host replication proteins at sites of viral replication in herpes-infected cells. Nature. 1991 Jan 31;349(6308):429-31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1671528
- ↑ Hunter T. Cooperation between oncogenes. Cell. 1991 Jan 25;64(2):249-70. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1988147
- ↑ Dynlacht BD. Retinoblastoma protein. Pol I gets repressed. Nature. 1995 Mar 9;374(6518):114. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7877677
Cavanaugh AH, Hempel WM, Taylor LJ, Rogalsky V, Todorov G, Rothblum LI. Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product. Nature. 1995 Mar 9;374(6518):177-80. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7877691 - ↑ 5.0 5.1 Cordon-Cardo C. Mutations of cell cycle regulators. Biological and clinical implications for human neoplasia. Am J Pathol. 1995 Sep;147(3):545-60. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7677168
- ↑ 6.0 6.1 White RJ, Trouche D, Martin K, Jackson SP, Kouzarides T. Repression of RNA polymerase III transcription by the retinoblastoma protein. Nature. 1996 Jul 4;382(6586):88-90. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8657311
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5925
- ↑ RB1base; Note: RB1 mutation db http://rb1-lsdb.d-lohmann.de/
- ↑ Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/RB1ID90.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=RB1
- ↑ Wikipedia; Note: retinoblastoma protein entry http://en.wikipedia.org/wiki/retinoblastoma_protein
- ↑ UniProt http://www.uniprot.org/uniprot/P06400.html
Database
- UniProt: http://www.uniprot.org/uniprot/P06400.html
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5925
- OMIM: https://mirror.omim.org/entry/109800
- OMIM: https://mirror.omim.org/entry/180200
- OMIM: https://mirror.omim.org/entry/259500
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5925