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Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1.

Harbour J.W., Luo R.X., Dei Santi A., Postigo A.A., Dean D.C.

We present evidence that phosphorylation of the C-terminal region of Rb by Cdk4/6 initiates successive intramolecular interactions between the C-terminal region and the central pocket. The initial interaction displaces histone deacetylase from the pocket, blocking active transcriptional repression by Rb. This facilitates a second interaction that leads to phosphorylation of the pocket by Cdk2 and disruption of pocket structure. These intramolecular interactions provide a molecular basis for sequential phosphorylation of Rb by Cdk4/6 and Cdk2. Cdk4/6 is activated early in G1, blocking active repression by Rb. However, it is not until near the end of G1, when cyclin E is expressed and Cdk2 is activated, that Rb is prevented from binding and inactivating E2F.

Cell 98:859-869(1999) [PubMed] [Europe PMC]

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