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 language | English (US) |
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Pages (from-to) | 38905-38911 |
Number of pages | 7 |
Journal | Journal of Biological Chemistry |
Volume | 275 |
Issue number | 49 |
DOIs | |
State | Published - Dec 8 2000 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology