Role of the p53-homologue p73 in EZF1-induced apoptosis

Most human cancers harbour aberrations of cell-cycle control(1), which resu lt in deregulated activity of the E2F transcription factors with concomitan t enhanced cell-cycle progression(2). Oncogenic signalling by E2F1 has rece ntly been linked to stabilization and activation of the tumour suppressor p 53 (refs 1,3,4). The p73 protein shares substantial sequence homology and f unctional similarity with p53 (refs 5-7). Hence, several previously conside red p53-independent cellular activities may be attributable to p73. Here we provide evidence that E2F1 directly activates transcription of TP73, leadi ng to activation of p53-responsive target genes and apoptosis. Disruption o f p73 function by a tumour-derived p53 mutant reduced E2F1-mediated apoptos is. Thus, p73 activation by deregulated E2F1 activity might constitute a p5 3-independent, anti-tumorigenic safeguard mechanism.