Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis.

XQ Qin, DM Livingston, WG Kaelin Jr… - Proceedings of the …, 1994 - pnas.org
XQ Qin, DM Livingston, WG Kaelin Jr, PD Adams
Proceedings of the National Academy of Sciences, 1994pnas.org
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 …
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.
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