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Using Kinetic Studies to Uncover New Rb Functions in Inhibiting Cell Cycle Progression
Peng Ji and Liang Zhu
volume 4 | issue 3
march 2005Pages: 373 - 375
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A well-established biological activity of the tumor suppressor Rb is blocking G1/S cell cycle progression when re-introduced into cultured Rb-deficient tumor cells. The best understood molecular mechanism underlying this function is that Rb binds the transcription factor E2F to repress expression of S phase genes such as cyclins E and A. A recent kinetic study of this model further revealed that Rb represses Skp2 to stabilize p27, which inhibits the kinase activity associated with cyclins E and A before the decline in their protein levels, to arrest the cell cycle. This p27-stabilizing function of Rb is retained in a clinical partial penetrance Rb mutant that is biochemically inactive for E2F repression, suggesting a mechanism for Rb-mediated inhibition of tumor progression.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.