Activation of initiator caspases through a stable dimeric intermediate

J Biol Chem. 2002 Dec 27;277(52):50761-7. doi: 10.1074/jbc.M210356200. Epub 2002 Oct 23.


Structural and biochemical studies have revealed that procaspases form dimers prior to proteolytic activation. How the two procaspases interact in the dimer is unclear. To study the mechanisms of dimer-dependent caspase activation we used a heterodimeric system so that two caspase molecules can be specifically brought together. Surprisingly, only one caspase partner in the dimer needs to be enzymatically active for caspase processing and activation to occur. Caspase activation is inefficient in the dimer in the absence of intramolecular processing, suggesting that caspase activation is initiated via intramolecular processing. Homodimerization of caspase-8 or caspase-9 leads to the formation of a stable dimeric complex. However, heterodimerization between caspase-8 and caspases-3, -9, or -10 failed to induce stable dimer formation or caspase activation. Our data suggest that the formation of a stable dimeric intermediate initiates caspase activation.

Publication types

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

MeSH terms

  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases / chemistry*
  • Caspases / metabolism*
  • Dimerization
  • Enzyme Activation
  • Enzyme Stability
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Tacrolimus Binding Proteins / metabolism
  • Transfection


  • Recombinant Proteins
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases
  • Tacrolimus Binding Proteins