Mechanisms of caspase activation.
The core effectors of apoptosis encompass proteolytic enzymes of the caspase family, which reside as latent precursors in most nucleated metazoan cells. A majority of studies on apoptosis are based on the assumption that caspase precursors are activated by cleavage, a common mechanism for most protease zymogen activations. Although this appears to be true for the executioner caspases, recent research points to a distinct activation mechanism for the initiator caspases that trigger the apoptotic pathways. This mechanism is proximity-induced dimerization without cleavage, and its elucidation has led to the revision of concepts of feedback regulation of apoptosis.
Boatright
Kelly M
KM
Program in Cell Death and Apoptosis Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Salvesen
Guy S
GS
D000818:Animals; D017209:Apoptosis; D053455:Caspase 10; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D019281:Dimerization; D004789:Enzyme Activation; D006801:Humans; D008954:Models, Biological
C505407:CASP3 protein, human; C505520:CASP7 protein, human; C505530:CASP8 protein, human; D053455:Caspase 10; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D020169:Caspases; C506438:CASP10 protein, human