Abstract
The transcription factor E2F-1 induces both cell-cycle progression and, in certain settings, apoptosis. E2F-1 uses both p53-dependent and p53-independent pathways to kill cells1,2,3,4,5,6,7,8. The p53-dependent pathway involves the induction by E2F-1 of the human tumour-suppressor protein p14ARF, which neutralizes HDM2 (human homologue of MDM2) and thereby stabilizes the p53 protein9. 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-defective 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 absence of p53.
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Acknowledgements
We thank A. Yang and F. McKeon for p73+/- mice and K. Baker for help with the apoptosis assays. M.I. is an American Cancer Society postdoctoral fellow. W.G.K. is a Howard Hughes Medical Institute assistant investigator.
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Irwin, M., Marin, M., Phillips, A. et al. Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature 407, 645–648 (2000). https://doi.org/10.1038/35036614
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DOI: https://doi.org/10.1038/35036614
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