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

Sayan, AE; Sayan, BS; Gogvadze, V; Dinsdale, G; Nyman, U; Hansen, TM; Zhivotovsky, B; Cohen, GM; Knight, RA; Melino, G

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.

• Journal Article Type: Article
• Online Publication Date: Mar 24, 2008
• Publication Date: Mar 24, 2008
• Deposit Date: Feb 6, 2023
• Journal: Oncogene
• Print ISSN: 0950-9232
• Electronic ISSN: 1476-5594
• Publisher: Nature Publishing Group
• Volume: 27
• Pages: 4363-4372
• DOI: https://doi.org/10.1038/onc.2008.64
• Publisher URL: https://doi.org/10.1038/onc.2008.64