A Role for p73 in p53-independent Apoptosis

Science's STKE  10 Oct 2000:
Vol. 2000, Issue 53, pp. tw7
DOI: 10.1126/stke.2000.53.tw7

Programmed cell death (apoptosis) can occur as a result of p53-dependent or p53-independent mechanisms. Now new evidence indicates that the p53-related protein p73 plays a direct role in p53-independent apoptosis mediated by the transcription factor E2F-1. Irwin et al. showed that the transcription factor E2F-1 activated a p73 promoter-driven gene reporter. Induced expression of E2F-1 in p53-deficient cells led to increased levels of p73 transcripts and protein; conversely, agents that lowered the levels of E2F-1 in cells, also reduced p73 levels. A p73 mutant (p73DD), that bound to wild-type p73 but did not support oligomerization, blocked p73-dependent transcription and apoptosis, even in the presence of increased amounts of E2F-1. Similar results on apoptotic inhibition were demonstrated in p73-/- mouse embryo fibroblasts. Lissy et al. examined p53-independent T cell receptor-mediated apoptosis and found that cell death occurring at the late G1 checkpoint was E2F-1-dependent. Onset of T cell receptor (TCR)-mediated apoptosis led to an abundance of increased p73, and was dependent on the presence of wild-type p73. Splenocytes from p73- or E2F-1-deficient mice were blocked from undergoing apoptosis, suggesting that p73 and E2F-1 work in the same pathway to mediate TCR-mediated apoptosis.

Irwin, M., Marin, M.C., Phillips, A.C., Seelan, R.S., Smith, D.I., Liu, W., Flores, E.R., Tsai, K.Y., Jacks, T., Vousden, K.H., and Kaelin, Jr., W.G. (2000) Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature 407: 645-648. [Online Journal]

Lissy, N.A., Davis, P.K., Irwin, M., Kaelin, W.G., and Dowdy, S.F. (2000) A common E2F-1 and p73 pathway mediates cell death induced by TCR activation. Nature 407: 642-645. [Online Journal]