Caspase-9 and APAF-1 form an active holoenzyme.
Autocatalytic activation of initiator caspases is the link between pro-apoptotic signals and the destruction machinery of apoptosis. Activation of caspase-9, which mediates oncogene and drug-induced apoptosis, requires binding to the protein APAF-1. We found that the proteolytic activity of caspase-9 in a complex with APAF-1 is several orders of magnitude higher than that of the free enzyme. Thus, this complex functions as a holoenzyme in which caspase-9 is the catalytic subunit and APAF-1 its allosteric regulator. We argue that caspase-9 is activated by allosteric regulation and suggest that this mechanism is common for other initiator caspases.
Rodriguez
J
J
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 USA.
Lazebnik
Y
Y
D000494:Allosteric Regulation; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D020134:Catalytic Domain; D002460:Cell Line; D002474:Cell-Free System; D002499:Centrifugation, Density Gradient; D006801:Humans; D007700:Kinetics; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D013379:Substrate Specificity
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D011506:Proteins; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases