Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade

✍ Scribed by Peng Li; Deepak Nijhawan; Imawati Budihardjo; Srinivasa M Srinivasula; Manzoor Ahmad; Emad S Alnemri; Xiaodong Wang

• Book ID: 117267385
• Publisher: Elsevier Science
• Year: 1997
• Tongue: English
• Weight: 804 KB
• Volume: 91
• Category: Article
• ISSN: 0092-8674
• DOI: 10.1016/s0092-8674(00)80434-1

✦ Synopsis

We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. Apaf-3 was identified as a member of the caspase family, caspase-9. Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. Activated caspase-9 in turn cleaves and activates caspase-3. Depletion of caspase-9 from S-100 extracts diminished caspase-3 activation. Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.