Abstract
We present evidence that Rb forms a repressor containing histone deacetylase (HDAC) and the hSWI/SNF nucleosome remodeling complex, which inhibits transcription of genes for cyclins E and A and arrests cells in the G1 phase of the cell cycle. Phosphorylation of Rb by cyclin D/cdk4 disrupts association with HDAC, relieving repression of the cyclin E gene and G1 arrest. However, the Rb-hSWI/SNF complex persists and is sufficient to maintain repression of the cyclin A and cdc2 genes, inhibiting exit from S phase. HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF then appear to maintain the order of cyclin E and A expression during the cell cycle, which in turn regulates exit from G1 and from S phase, respectively.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites
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CDC2-CDC28 Kinases*
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Carrier Proteins / metabolism
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Cell Cycle
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Cell Division
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Cyclin A / genetics
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Cyclin D
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Cyclin E / genetics
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Cyclin-Dependent Kinases / metabolism
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Cyclins / metabolism
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DNA Helicases
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Enzyme Inhibitors / pharmacology
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G1 Phase*
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Histone Deacetylase Inhibitors
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Histone Deacetylases / metabolism*
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Humans
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Hydroxamic Acids / pharmacology
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Nuclear Proteins / metabolism*
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Phosphorylation
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Promoter Regions, Genetic
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins*
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Repressor Proteins / metabolism*
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Retinoblastoma Protein / metabolism*
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S Phase*
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transfection
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Tumor Cells, Cultured
Substances
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Carrier Proteins
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Cyclin A
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Cyclin D
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Cyclin E
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclins
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Nuclear Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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Retinoblastoma Protein
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SMARCA2 protein, human
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Transcription Factors
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trichostatin A
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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CDK2 protein, human
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CDK4 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases
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Histone Deacetylases
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SMARCA4 protein, human
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DNA Helicases