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Biochim Biophys Acta. 2001 Mar 21;1471(3):M123-33.

Regulation of the retinoblastoma tumor suppressor protein by cyclin/cdks.

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Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.


The retinoblastoma tumor suppressor protein (pRB) is a paradigm for understanding cell cycle- and proliferation-dependent transcription and how deregulation of this process contributes to the neoplastic process in humans. The ability of pRB to regulate transcription, and consequently cell proliferation and differentiation, is regulated by the activity of cyclin/cdks. In general, phosphorylation of pRB by cyclin/cdks inactivates pRB-mediated transcriptional inhibition and growth suppression. However, it is apparent that pRB is a multi-functional protein that can inhibit transcription through various mechanisms. This review focuses on recent data to suggest that different pRB functions are progressively and cooperatively inactivated by multiple cyclin/cdk complexes during G1- and S-phase. The implications of such a model for pRB-mediated tumor suppression are discussed.

[Indexed for MEDLINE]

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