Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis.Xu Qin, David M. Livingston, William G. Kaelin et al.|Proceedings of the National Academy of Sciences|1994 E2F-1 is a transcription factor suspected of activating genes required for S phase and a known target for the action of RB, the retinoblastoma 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 species of p53. In contrast, coexpression of a naturally occurring loss-of-function RB mutant or wild-type p53 did not suppress the induction of apoptosis under these conditions. Thus, deregulated E2F-1 activity gives rise to proliferative and apoptotic signals. p53 appears to participate in the execution of the latter.
Identification of a growth suppression domain within the retinoblastoma gene product.To date, all naturally occurring retinoblastoma susceptibility gene (RB) mutations known to be compatible with stable protein expression map to the T/E1A and cellular protein-binding region (the "pocket" domain). This domain extends from residue 379 to 792. When full-length RB and certain truncated forms were synthesized in human RB -/- cells, we found that the minimal region necessary for overt growth suppression extended from residue 379 to 928. A functional pocket domain and sequences extending from the carboxy-terminal boundary of the pocket to the carboxyl terminus of the protein were both necessary for growth suppression. Both sets of sequences were also required for E2F binding; hence, the two functions may be linked.