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.

Citation

Sayan, A., Sayan, B., Gogvadze, V., Dinsdale, G., Nyman, U., Hansen, T., …Melino, G. (2008). p73 and caspase-cleaved p73 fragments localize to mitochondria and augment TRAIL-induced apoptosis. Oncogene, 27, 4363-4372. https://doi.org/10.1038/onc.2008.64

• 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