Molecular ordering of apoptotic mammalian CED-3/ICE-like proteases

J Biol Chem. 1996 Aug 30;271(35):20977-80. doi: 10.1074/jbc.271.35.20977.


Apoptosis is executed by cysteine proteases belonging to the CED-3/ICE family, which, unlike other mammalian cysteine proteases, cleave their substrates following aspartate residues. Proteases belonging to this family exist in the cytosol as zymogens that require accurate processing at internal aspartate residues to generate the two-chain active enzymes. As such, CED-3/ICE family members are capable of activating each other in a manner analogous to the protease zymogens of the coagulation or complement cascades. At present, it is unknown whether such mutual processing exists in vivo, and if so whether it is sequential, implying an order to the death pathway. Using a cell-free apoptosis system, recombinant ICE proteases and both biochemical and morphological criteria, we demonstrate an ordering of the mammalian ICEs that are most related to the Caenorhabditis elegans death protease CED-3.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans Proteins
  • Caspases*
  • Cell Line
  • Cysteine Endopeptidases / genetics*
  • Cysteine Endopeptidases / metabolism
  • Enzyme Activation
  • Enzyme Precursors / metabolism
  • HeLa Cells
  • Helminth Proteins / genetics*
  • Helminth Proteins / metabolism
  • Humans
  • Hydrolysis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Substrate Specificity


  • Caenorhabditis elegans Proteins
  • Enzyme Precursors
  • Helminth Proteins
  • Recombinant Proteins
  • Caspases
  • Cysteine Endopeptidases
  • ced-3 protein, C elegans