The E2F family of transcription factors plays an essential role in promotin
g cell cycle progression, and one member of the family, E2F-1, is also capa
ble of inducing apoptosis. We show here that E2F-1 can induce apoptosis by
a death receptor-dependent mechanism, by downregulating TRAF2 protein level
s and inhibiting activation of antiapoptotic signals including NF-kappa B.
In this way, E2F-1 expression can lead to the sensitization of cells to apo
ptosis by a number of agents independently of p53. Deregulation of E2F-1 ac
tivity occurs in the majority of human tumors, and the ability of E2F-1 to
inhibit antiapoptotic signaling may contribute to the enhanced sensitivity
of transformed cells to chemotherapeutic agents.