✦ LIBER ✦

Functions of the retinoblastoma protein

✍ Scribed by William G. Kaelin Jr.

Publisher: John Wiley and Sons
Year: 1999
Tongue: English
Weight: 182 KB
Volume: 21
Category: Article
ISSN: 0265-9247
DOI: 10.1002/(sici)1521-1878(199911)21:11<950::aid-bies7>3.0.co;2-d

No coin nor oath required. For personal study only.

✦ Synopsis

The retinoblastoma protein (pRB) can both positively and negatively regulate transcription. The former correlates with its ability to promote differentiation and the latter with its ability to regulate entry into S-phase. pRB negatively regulates transcription by forming complexes with members of the E2F transcription factor family. These complexes, when bound to E2F sites within certain target genes, actively repress transcription through a variety of mechanisms including physical interaction with adjacent transcriptional activation domains and recruitment of proteins that directly, or indirectly, lead to histone deacetylation. pRB function is, in turn, modulated by phosphorylation mediated by cyclin-dependent kinases. Emerging data suggest that combinatorial control of pRB function may be achieved through the use of different phosphoacceptor sites, different cyclin/cdk docking sites, and different cyclin/cdk complexes. The untimely activation of E2F responsive genes can induce apoptosis. This comes about at least partly through the induction of ARF, which leads to the stabilization and activation of p53.

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