p130/E2F4 binds to and represses the cdc2 promoter in response to p53

p53 represses the transcription of cdc2 and cyclin B1, causing loss of Cdc2 activity and Cf, arrest. Here we show that the region -22 to -2 of the cdc 2 promoter called the R box is required for repression by p53 but not for b asal promoter activity. The R box confers p53-dependent repression on heter ologous promoters and binds to p130/E2F4 in response to overexpression of p 53. 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 de pendent kinase activity, enhancing the binding of p130 and E2F4, which toge ther bind to and repress the cdc2 promoter.