E2F-1 potentiates cell death by blocking antiapoptotic signaling pathways

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.