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

Academic Article


  • 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.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Ding HF; Lin YG; McGill G; Juo P; Zhu H; Blenis J; Yuan J; Fisher DE
  • Start Page

  • 38905
  • End Page

  • 38911
  • Volume

  • 275
  • Issue

  • 49