Oligomerization and activation of caspase-9, induced by Apaf-1 CARD

Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4197-202. doi: 10.1073/pnas.072544399. Epub 2002 Mar 19.


Apaf-1 facilitates the proteolytic activation of procaspase-9 and maintains the hyperactive state of the processed caspase-9. The underlying molecular mechanisms for these activities remain poorly characterized. Here we report that the isolated Apaf-1 caspase recruitment domain (CARD) forms a large hetero-oligomer with the active caspase-9. The catalytic activity of caspase-9 is significantly enhanced in this complex, demonstrating that Apaf-1 CARD allosterically up-regulates caspase-9 activity. Point mutations that inactivate the interactions between Apaf-1 CARD and the prodomain of caspase-9 also abolished the formation of this complex. Based on these observations, we discuss the implications of this complex on the observed Apaf-1 function.

Publication types

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

MeSH terms

  • Apoptotic Protease-Activating Factor 1
  • Caspase 9
  • Caspases / chemistry*
  • Caspases / metabolism
  • Dimerization
  • Enzyme Activation
  • Models, Structural
  • Proteins / chemistry*
  • Proteins / physiology


  • Apoptotic Protease-Activating Factor 1
  • Proteins
  • Caspase 9
  • Caspases