Activation of initiator caspases through a stable dimeric intermediate

Min Chen, Aaron Orozco, David M Spencer, Jin Wang

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)50761-7
Number of pages7
JournalThe Journal of biological chemistry
Issue number52
StatePublished - Dec 27 2002


  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases
  • Dimerization
  • Enzyme Activation
  • Enzyme Stability
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Recombinant Proteins
  • Tacrolimus Binding Proteins
  • Transfection
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.


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