A role for E2F1 in Ras activation of p21((WAF1/CIP1)) transcription

We recently reported that E2F1 could transactivate the p21 promoter via cis -acting elements between -119 to +16 bp of the p21 gene. Here we show that activated V12-H-Ras can induce the p21 promoter through the same region of the p21 promoter by a p53-independent mechanism in NIH3T3 cells. In contras t, activated Ras was not able to induce the p21 promoter in E2F1(-/-) fibro blasts, suggesting that E2F1 is required for induction of the p21 promoter by activated Ras, Cotransfection of increasing concentrations of dominant n egative E2F1 alone, or with dominant negative DP1 into NIH3T3 cells suppres sed induction of the p21 promoter by activated Pas. These data suggest that p53-independent induction of the p21 promoter by activated Ras is mediated at least in part by E2F1.