title: Activation of caspases triggered by cytochrome c in vitro.
abstract: Previous studies have shown that Apaf-1 and caspase-9 in the presence of cytochrome c and dATP can form an initiating complex for an apoptotic protease cascade. We have developed a cytochrome c-dependent in vitro system in which caspases downstream of this initiation complex are activated. The activation of caspase-9 from zymogen form to active dimeric protease requires intrinsic enzymatic activity. In contrast, caspase-3 and caspase-7 zymogens are proteolytically processed by active caspase-9. Activation of the above caspases is blocked by a dominant negative form of caspase-9. The in vitro system displays surprising specificity in that other caspases, including 1, 2, 4, 8, 10, and 13, are not activated.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
authors.forename: G
authors.initials: G
authors.lastname: Pan
authors.forename: E W
authors.initials: EW
authors.lastname: Humke
authors.forename: V M
authors.initials: VM
authors.lastname: Dixit
mesh_terms: D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases; D002474:Cell-Free System; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003574:Cytochrome c Group / Q000502:physiology*; D019281:Dimerization; D004789:Enzyme Activation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D013329:Structure-Activity Relationship
chemical_list: D053477:Apoptotic Protease-Activating Factor 1; D003574:Cytochrome c Group; D011506:Proteins; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases