Most human cancers harbour aberrations of cell-cycle control1,
which result in deregulated activity of the E2F transcription factors with
concomitant enhanced cell-cycle progression2. Oncogenic signalling
by E2F1 has recently been linked to stabilization and activation of the tumour
suppressor p53 (refs 1,3,4). The p73 protein shares substantial sequence homology
and functional similarity with p53 (refs 5−7
). Hence, several previously considered p53-independent cellular
activities may be attributable to p73. Here we provide evidence that E2F1
directly activates transcription of TP73, leading to activation of
p53-responsive target genes and apoptosis. Disruption of p73 function by a
tumour-derived p53 mutant reduced E2F1-mediated apoptosis. Thus, p73 activation
by deregulated E2F1 activity might constitute a p53-independent, anti-tumorigenic
safeguard mechanism.
