E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation

E2F-1 induces p53 accumulation and E2F-1 and p53 form a physical complex, w hich affects the ability of E2F-1 to activate transcription. We mapped the domains on E2F-1 that interact with p53 and found two p53-binding domains. To understand the functional consequences of the E2F-1/p53 association on p 53 activities we identified the domains of E2F-1 that were responsible for the accumulation of p53. Unexpectedly, we found that the E2F-1 transactivat ion domain was dispensable for p53 induction. By contrast, further deletion of the DP-1 interaction/'marked' box domain eliminated p53 accumulation. R adiolabeling pulse/chase analysis demonstrated that E2F-1 caused post-trans lational stabilization of p53. Although E2F-1 caused the stabilization of p 53, E2F-1 expression impaired p53-dependent transactivation. Thus, the E2F- 1:p53 interaction may provide a checkpoint function to inactivate overactiv e E2F-1, but the association may also inactivate p53 transactivation to all ow cell cycle progression.