CASPASE-9, BCL-X-L, AND APAF-1 FORM A TERNARY COMPLEX

Genetic analysis of apoptosis in the nematode Caenorhabditis elegans h as revealed the cell death machine to be composed of three core intera cting components. CED-4 (equivalent to mammalian Apaf-1) is a nucleoti de binding molecule that complexes with the zymogen form of the death protease CED-3, leading to its autoactivation and cell death, CED-9 bl ocks death by complexing with CED-4 and attenuating its ability to pro mote CED-3 activation, An equivalent ternary complex was found to be p resent in mammalian cells involving Apaf-1, the mammalian death protea se caspase-9, and Bcl-X-L, an anti-apoptotic member of the Bcl-2 famil y, Consistent with a central role for caspase-9, a dominant negative f orm effectively inhibited cell death initiated by a wide variety of in ducers.