E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos

The E2F transcription factors are thought to be key downstream targets of the retinoblastoma protein (pRB) tumor suppressor. It is widely believed that E2F1, E2F2, and E2F3 can all activate cellular proliferation but that E2F1 is the specific inducer of apoptosis. Here we show that the E2f3 mutation completely suppresses both the inappropriate proliferation and the p53-dependent apoptosis arising in the Rb mutant embryos. Through the analysis of Rb-/-;E2f3(+/-) embryos, we have been able to separate E2F3's role in the induction of apoptosis from its ability to induce proliferation, Thus, contrary to the prevailing view of E2F action, E2F3 makes a major contribution to the apoptosis resulting from pRB loss.