Role for the p53 homologue p73 in E2F-1-induced apoptosis

The transcription factor E2F-1 induces both cell-cycle progression and, in certain settings, apoptosis. E2F-1 uses both p53-dependent and p53-independ ent pathways to kill cells(1-8). The p53-dependent pathway involves the ind uction by E2F-1 of the human tumour-suppressor protein p14ARF, which neutra lizes HDM2 (human homologue of MDM2) and thereby stabilizes the p53 protein (9). Here we show that E2F-1 induces the transcription of the p53 homologue p73. Disruption of p73 function inhibited E2F-1-induced apoptosis in p53-d efective tumour cells and in p53(-/-) mouse embryo fibroblasts. We conclude that activation of p73 provides a means for E2F-1 to induce death in the a bsence of p53.