DEREGULATED TRANSCRIPTION FACTOR E2F-1 EXPRESSION LEADS TO S-PHASE ENTRY AND P53-MEDIATED APOPTOSIS

E2F-1 is a transcription factor suspected of activating genes required for S phase and a known target for the action of RB, the retinoblasto ma gene product. Its induction in quiescent fibroblasts led to S-phase entry followed by apoptosis. E2F-1-mediated apoptosis was suppressed by coexpression of wild-type RB or a transdominant negative mutant spe cies of p53. In contrast, coexpression of a naturally occurring loss-o f-function RB mutant or wild-type p53 did not suppress the induction o f apoptosis under these conditions. Thus, deregulated E2F-1 activity g ives rise to proliferative and apoptotic signals. p53 appears to parti cipate in the execution of the latter.