Cdk-mediated phosphorylation of pRB regulates HDAC binding in vitro.

Retinoblastoma protein (pRB) controls the G1/S transition in the cell cycle by binding and inactivating E2F transcription factor. pRB changes the chromatin structure at the E2F-responsive promoter by recruiting histone deacetylase (HDAC) to the pRB-E2F complex, thus controlling the transcriptional activity of E2F. Cyclin-dependent kinases (Cdks) phosphorylate pRB and disrupt ...
association between pRB and E2F. We investigated the effects of pRB phosphorylation on HDAC-1 binding in vitro. Phosphorylation of pRB by Cdk4-cyclin D2, Cdk2-cyclin E, and Cdk2-cyclin A inhibited association of pRB with HDAC. Among these Cdks, Cdk4-cyclin D2 showed particularly effective inhibition of pRB-HDAC complex formation. Using pRB mutants with various deletions in the N- and C-terminal domains, we found that both the pocket and C-terminal domains are important for regulating association between pRB and HDAC.
Mesh Terms:
Cell Cycle Proteins, Cyclin-Dependent Kinases, DNA-Binding Proteins, E2F Transcription Factors, Epigenesis, Genetic, Histone Deacetylase 1, Histone Deacetylases, Humans, Phosphorylation, Protein Binding, Protein Structure, Tertiary, Retinoblastoma Protein, Threonine, Transcription Factors
Biochem. Biophys. Res. Commun.
Date: Mar. 26, 2004
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