Thursday 2 October 2003
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.
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
RB/E2F pathway (P16(INK4A)-CDK4/6-RB)
Loss of retinoblastoma protein expression in spindle cell/pleomorphic lipomas and cytogenetically related tumors: an immunohistochemical study with diagnostic implications. Chen BJ, Mariño-Enríquez A, Fletcher CD, Hornick JL. Am J Surg Pathol. 2012 Aug;36(8):1119-28. PMID: 22790852
Jones EE, Wells SI. Cervical cancer and human papillomaviruses: inactivation of retinoblastoma and other tumor suppressor pathways. Curr Mol Med. 2006 Nov;6(7):795-808. PMID: 17100604
Wikenheiser-Brokamp KA. Retinoblastoma regulatory pathway in lung cancer. Curr Mol Med. 2006 Nov;6(7):783-93. PMID: 17100603
Pacal M, Bremner R. Insights from animal models on the origins and progression of retinoblastoma. Curr Mol Med. 2006 Nov;6(7):759-81. PMID: 17100602
Korenjak M, Brehm A. The retinoblastoma tumour suppressor in model organisms—new insights from flies and worms. Curr Mol Med. 2006 Nov;6(7):705-11. PMID: 17100596
Classon M, Harlow E. The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer. 2002 Dec;2(12):910-7. PMID: 12459729
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