INDUCTION OF DNA-SYNTHESIS AND APOPTOSIS ARE SEPARABLE FUNCTIONS OF E2F-1

The family of E2F transcription factors have an essential role in medi ating cell cycle progression, and recently, one of the E2F protein fam ily, E2F-1, has been shown to participate in the induction of apoptosi s. Cooperation between E2F and the p53 tumor suppressor protein in thi s apoptotic response had led to the suggestion that cell cycle progres sion induced by E2F-1 expression provides an apoptotic signal when pla ced in conflict with an arrest to cell cycle progression, such as prov ided by p53. We show here that although apoptosis is clearly enhanced by p53, E2F-1 can induce significant apoptosis in the absence of p53. furthermore, this apoptotic function of E2F-1 is separable from the ab ility to accelerate entry into DNA synthesis, Analysis of E2F-1 mutant s indicates that although DNA-binding is required, transcriptional tra nsactivation is not necessary for the induction of apoptosis by E2F-1, suggesting that it may be mediated through alleviation of E2F-depende nt transcriptional repression. These results indicate that E2F-1 can s how independent cell cycle progression and apoptotic functions, consis tent with its putative role as a tumor suppressor.