Ding, Han-FeiLin, Yi-LingMcGill, GaëlJuo, PeterZhu, HongBlenis, JohnYuan, JunyingFisher, David E.2019-10-052000Ding, Han-Fei, Yi-Ling Lin, Gaël McGill, Peter Juo, Hong Zhu, John Blenis, Junying Yuan, and David E. Fisher. 2000. “Essential Role for Caspase-8 in Transcription-Independent Apoptosis Triggered by p53.” Journal of Biological Chemistry 275 (49): 38905–11. https://doi.org/10.1074/jbc.m004714200.0021-92581083-351Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483491p53'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 wildtype 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.en-USJournal Article2019-10-0510.1074/jbc.M004714200