P73 and caspase-cleaved p73 fragments localize to mitochondria and augment TRAIL-induced apoptosis

Sayan, A.E., Sayan, B.S., Gogvadze, V., Dinsdale, D., Nyman, U., Hansen, T.M., Zhivotovsky, B., Cohen, G.M., Knight, R.A. and Melino, G. (2008) P73 and caspase-cleaved p73 fragments localize to mitochondria and augment TRAIL-induced apoptosis. Oncogene, 27 (31), 4363-4372. (doi:10.1038/onc.2008.64). (PMID:18362891)

Abstract

The p73 protein, a member of the p53 family, has both developmental and tumorigenic functions. Here we show that p73 is cleaved by caspase-3 and -8 both in vitro and in vivo during apoptosis elicited by DNA-damaging drugs and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor ligation. TAp73 and some of its cleavage products are localized to mitochondria. siRNA-mediated downregulation of p73 expression induced a small but significant change in the susceptibility of HCT116 cells to TRAIL-induced apoptosis. A transcription-deficient mutant of TAp73 enhanced TRAIL-induced apoptosis suggesting that p73 protein has transcription-independent functions during death receptor-mediated apoptosis. Additionally, recombinant p73 protein induced cytochrome c release from isolated mitochondria providing evidence that nonnuclear p73 may have additional functions in the progression of apoptosis.

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Contributors

Author: A.E. Sayan

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