Autoproteolytic activation of pro-caspases by oligomerization

Mol Cell. 1998 Jan;1(2):319-25. doi: 10.1016/s1097-2765(00)80032-5.

Abstract

Initiation of apopotosis requires the conversion of procaspases to mature caspases. Here we show that oligomerization of pro-caspases is sufficient to induce proteolytic generation of mature caspase subunits and activation of their cell death activity. Deletion of the protein interaction motif DED from pro-caspase-8 greatly suppresses its apoptotic activity. Cell death activity can be restored by oligomerization of pro-caspase-8 protease domains by two heterologous inducible oligomerization systems. Induced oligomerization also activates the apoptotic activity of pro-caspase-1 but not pro-caspase-3. In vitro, oligomerization leads to pro-caspase processing to from the mature caspase subunits; this processing requires the intrinsic caspase activity of zymogens and proceeds via a novel order of cleavage events.

Publication types

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

MeSH terms

  • Apoptosis / physiology*
  • Caspase 1
  • Caspase 3
  • Caspases*
  • Cell-Free System / enzymology
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / metabolism*
  • Dimerization
  • Enzyme Precursors / chemistry
  • Enzyme Precursors / metabolism*
  • Fas Ligand Protein
  • HeLa Cells
  • Humans
  • Membrane Glycoproteins / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Transfection

Substances

  • Enzyme Precursors
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases
  • Caspase 1