Regulation of CD95/Fas signaling at the DISC

Cell Death Differ. 2012 Jan;19(1):36-41. doi: 10.1038/cdd.2011.155. Epub 2011 Nov 11.

Abstract

CD95 (APO-1/Fas) is a member of the death receptor (DR) family. Stimulation of CD95 leads to induction of apoptotic and non-apoptotic signaling pathways. The formation of the CD95 death-inducing signaling complex (DISC) is the initial step of CD95 signaling. Activation of procaspase-8 at the DISC leads to the induction of DR-mediated apoptosis. The activation of procaspase-8 is blocked by cellular FLICE-inhibitory proteins (c-FLIP). This review is focused on the role in the CD95-mediated signaling of the death effector domain-containing proteins procaspase-8 and c-FLIP. We discuss how dynamic cross-talk between procaspase-8 and c-FLIP at the DISC regulates life/death decisions at CD95.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis*
  • CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism*
  • Caspase 8 / metabolism*
  • Caspase 9 / metabolism
  • Death Domain Receptor Signaling Adaptor Proteins / metabolism*
  • Fas-Associated Death Domain Protein / metabolism
  • Humans
  • Protein Structure, Tertiary
  • Signal Transduction
  • fas Receptor / metabolism*

Substances

  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Death Domain Receptor Signaling Adaptor Proteins
  • FAS protein, human
  • Fas-Associated Death Domain Protein
  • fas Receptor
  • Caspase 8
  • Caspase 9