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Papers In Press, published online ahead of print October 13, 2000
Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195
Corresponding Author: starkg{at}ccf.org
p53 represses the transcription of cdc2 and cyclin B1, causing loss of Cdc2 activity and G2 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.
J. Biol. Chem, 10.1074/jbc.M005101200
Submitted on June 13, 2000
Revised on October 11, 2000
Accepted on October 12, 2000
p130/E2F4 binds to and represses the cdc2 promoter in response to p53
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