RB
Cell cycle regulation
In a resting cell, RB is a component of the E2F/DP1/RB complex, which represses gene transcription through the recruitment of histone deacetylase, an enzyme that alters the conformation of chromatin, making it more compact.
Phosphorylation of RB by cyclin D-CDK4 removes histone deacetylase from chromatin, allowing the activation of E2F transcriptional activity (RB can also be phosphorylated by cyclin E-CDK2).
E2F-mediated transcription of cyclins E and A, and of genes required for DNA replication, permit the passage through the G1 restriction point.
Tumor predisposition
retinoblastoma
post-radiation osteosarcoma
Pathology
germline mutations in familial retinoblastoma
germline and somatic mutations in sporadic retinoblastoma
somatic mutations in post-radiation osteosarcoma
inactivation of RB protein by HPV-E6 and HPV-E7 oncoproteins
Features
RB/E2F pathway (P16(INK4A)-CDK4/6-RB)
References
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Liu H, Dibling B, Spike B, Dirlam A, Macleod K. New roles for the RB tumor suppressor protein. Curr Opin Genet Dev. 2004 Feb;14(1):55-64. PMID: 15108806
Chau BN, Wang JY. Coordinated regulation of life and death by RB. Nat Rev Cancer. 2003 Feb;3(2):130-8. PMID: 12563312
Classon M, Harlow E. The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer. 2002 Dec;2(12):910-7. PMID: 12459729
Nevins JR. The Rb/E2F pathway and cancer. Hum Mol Genet. 2001 Apr;10(7):699-703. PMID: 11257102
Korenjak M, Brehm A. E2F-Rb complexes regulating transcription of genes important for differentiation and development. Curr Opin Genet Dev. 2005 Oct;15(5):520-7. PMID: 16081278
Blais A, Dynlacht BD. Hitting their targets: an emerging picture of E2F and cell cycle control. Curr Opin Genet Dev. 2004 Oct;14(5):527-32. PMID: 15380244
Nevins JR. The Rb/E2F pathway and cancer. Hum Mol Genet. 2001 Apr;10(7):699-703. PMID: 11257102