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

A. E. Sayan, B. S. Sayan, V. Gogvadze, D. Dinsdale, U. Nyman, T. M. Hansen, B. Zhivotovsky, G. M. Cohen, R. A. Knight, G. Melino

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4363-4372
Number of pages10
JournalOncogene
Volume27
Issue number31
DOIs
Publication statusPublished - Jul 17 2008

Keywords

  • Apoptosis
  • Mitochondria
  • p53
  • p73
  • TRAIL
  • Transcription independent

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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