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

Abstract

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.

Keywords

BiologyCaspaseApoptosisCytochrome cApoptosomeCascadeCell biologyProteaseCytochromeCaspase-9Caspase 3Molecular biologyBiochemistryProgrammed cell deathEnzyme

MeSH Terms

Amino Acid SequenceApoptosisApoptotic Protease-Activating Factor 1Binding SitesBreast NeoplasmsCaspase 3Caspase 9CaspasesCell LineCysteine EndopeptidasesCytochrome c GroupDeoxyadenine NucleotidesEnzyme ActivationEpithelial CellsHeLa CellsHumansKidneyModelsChemicalMolecular Sequence DataMultienzyme ComplexesMutationProtein BindingProteinsTumor CellsCultured

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Publication Info

Year: 1997
Type: article
Volume: 91
Issue: 4
Pages: 479-489
Citations: 7186
Access: Closed

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APA Style

                            
                                
                                    Peng Li, 
                                
                                    Deepak Nijhawan, 
                                
                                    I. Imawati Budihardjo
                                
                                et al.
                            
                            (1997). 
                            Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade. 
                            Cell
                            , 91
                            (4)
                            , 479-489.
                            https://doi.org/10.1016/s0092-8674(00)80434-1
                        

Identifiers

DOI: 10.1016/s0092-8674(00)80434-1
PMID: 9390557

Data Quality

Data completeness: 86%