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

J W Harbour·R X Luo·A Dei Santi·A A Postigo·D C Dean
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Abstract

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.

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CDC2-CDC28 KinasesCarrier ProteinsCell Cycle ProteinsCyclin ECyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Cyclin-Dependent KinasesDNA-Binding ProteinsE2F Transcription FactorsFemaleG1 PhaseGene Expression RegulationHistone DeacetylasesHumansLysineMutationPeptide FragmentsPhosphorylationProtein BindingProtein ConformationProtein Serine-Threonine KinasesProto-Oncogene ProteinsRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Transcription Factor DP1Transcription FactorsTranscription, GeneticTumor Cells, CulturedJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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J W Harbour, R X Luo, A Dei Santi, A A Postigo, D C Dean. 1999-09-17. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1.. https://doi.org/10.1016/s0092-8674(00)81519-6

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