Essential role for caspase-8 in transcription-independent apoptosis triggered by p53

Hanfei Ding, Yi G. Lin, Gaël McGill, Peter Juo, Hong Zhu, John Blenis, Junying Yuan, David E. Fisher

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117 Scopus citations

Abstract

p53's Dual regulation of arrest versus apoptosis may underlie tumor-selective effects of anti-cancer therapy. p53's apoptotic effect has been suggested to involve both transcription-dependent and -independent mechanisms. It is shown here that caspase-8 is activated early in cells undergoing p53-mediated apoptosis and in S100 cell-free extracts that recapitulate transcription-independent apoptosis. Depletion or inactivation of caspase-8 either in cells or cell-free extracts completely prevents this transcription-independent apoptosis and significantly attenuates overall death induced by wild-type p53. Importantly, caspase-8 activation appears to be independent of FADD, and caspase-8 is found in a novel 600-kDa complex following p53 activation. These findings highlight the roles of both transcription-dependent and -independent apoptosis by p53 and identify an essential role for caspase-8 in the transcription-independent pathway.

Original languageEnglish (US)
Pages (from-to)38905-38911
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number49
DOIs
Publication statusPublished - Dec 8 2000

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ding, H., Lin, Y. G., McGill, G., Juo, P., Zhu, H., Blenis, J., ... Fisher, D. E. (2000). Essential role for caspase-8 in transcription-independent apoptosis triggered by p53. Journal of Biological Chemistry, 275(49), 38905-38911. https://doi.org/10.1074/jbc.M004714200