Abstract
p53 represses the transcription of cdc2 and cyclin B1, causing loss of Cdc2 activity and G(2) arrest. Here we show that the region -22 to -2 of the cdc2 promoter called the R box is required for repression by p53 but not for basal promoter activity. The R box confers p53-dependent repression on heterologous promoters and binds to p130/E2F4 in response to overexpression of p53. R box-dependent repression requires p21/waf1, and overexpression of p21/waf1 also represses the cdc2 promoter. These observations suggest that p53 represses the cdc2 promoter by inducing p21/waf1, which inhibits cyclin-dependent kinase activity, enhancing the binding of p130 and E2F4, which together bind to and repress the cdc2 promoter.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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CDC2-CDC28 Kinases*
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Cell Line
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / metabolism*
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DNA
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DNA-Binding Proteins / metabolism*
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E2F4 Transcription Factor
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Molecular Sequence Data
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Promoter Regions, Genetic*
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Protein Binding
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Repressor Proteins / metabolism
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Transcription Factors / metabolism*
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Transcription, Genetic
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Tumor Suppressor Protein p53 / metabolism*
Substances
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DNA-Binding Proteins
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E2F4 Transcription Factor
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Repressor Proteins
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Transcription Factors
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Tumor Suppressor Protein p53
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DNA
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases