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

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.
Mesh Terms:
CDC2-CDC28 Kinases, Carrier Proteins, Cell Cycle Proteins, Cyclin E, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Cyclin-Dependent Kinases, DNA-Binding Proteins, E2F Transcription Factors, Female, G1 Phase, Gene Expression Regulation, Histone Deacetylases, Humans, Lysine, Mutation, Peptide Fragments, Phosphorylation, Protein Binding, Protein Conformation, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Retinoblastoma Protein, Retinoblastoma-Binding Protein 1, Transcription Factor DP1, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured
Date: Sep. 17, 1999
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