Caspase-8 in apoptosis: the beginning of "the end"?

IUBMB Life. 2000 Aug;50(2):85-90. doi: 10.1080/713803693.


Caspase-8 is a member of the cysteine proteases, which are implicated in apoptosis and cytokine processing. Like all caspases, caspase-8 is synthesized as an inactive single polypeptide chain zymogen procaspase and is activated by proteolytic cleavage, through either autoactivation after recruitment into a multimeric complex or trans-cleavage by other caspases. Thus, ligand binding-induced trimerization of death receptors results in recruitment of the receptor-specific adapter protein Fas-associated death domain (FADD), which then recruits caspase-8. Activated caspase-8 is known to propagate the apoptotic signal either by directly cleaving and activating downstream caspases or by cleaving the BH3 Bcl2-interacting protein, which leads to the release of cytochrome c from mitochondria, triggering activation of caspase-9 in a complex with dATP and Apaf-1. Activated caspase-9 then activates further "downstream caspases," including caspase-8. Knockout data indicate that caspase-8 is required for killing induced by the death receptors Fas, tumor necrosis factor receptor 1, and death receptor 3. Moreover, caspase-8-/- mice die in utero as a result of defective development of heart muscle and display fewer hematopoietic progenitor cells, suggesting that the FADD/caspase-8 pathway is absolutely required for growth and development of specific cell types.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis*
  • Apoptotic Protease-Activating Factor 1
  • Arabidopsis Proteins*
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism*
  • Caspases / physiology*
  • Cytochrome c Group / metabolism
  • Enzyme Activation
  • Fatty Acid Desaturases / metabolism*
  • Humans
  • Ligands
  • Mice
  • Mice, Knockout
  • Proteins / metabolism


  • APAF1 protein, human
  • Apaf1 protein, mouse
  • Apoptotic Protease-Activating Factor 1
  • Arabidopsis Proteins
  • Cytochrome c Group
  • Ligands
  • Proteins
  • Adenosine Triphosphate
  • Fatty Acid Desaturases
  • Fad7 protein, Arabidopsis
  • CASP8 protein, human
  • CASP9 protein, human
  • Casp8 protein, mouse
  • Casp9 protein, mouse
  • Caspase 8
  • Caspase 9
  • Caspases