Caspases - controlling intracellular signals by protease zymogen activation.
Animal development and homeostasis is a balance between cell proliferation and cell death. Physiologic, and sometimes pathologic, cell death - apoptosis - is driven by activation of a family of proteases known as the caspases, present in almost all nucleated animal cells. The enzymatic properties of these proteases are governed by a dominant specificity for substrates containing Asp, and by the use of a Cys side chain for catalyzing peptide bond cleavage. The primary specificity for Asp turns out to be very rare among proteases, and currently the only other known mammalian proteases with the same primary specificity is the physiological caspase activator granzyme B. Like most other proteases, the caspases are synthesized as inactive zymogens whose activation requires limited proteolysis or binding to co-factors. To transmit the apoptotic execution signal, caspase zymogens are sequentially activated through either an intrinsic or an extrinsic pathway. The activation of caspases at the apex of each pathway, the initiators, occurs by recruitment to specific adapter molecules through homophilic interaction domains, and the activated initiators directly process the executioner caspases to their catalytically active forms. In the present communication we review the different mechanisms underlying the selective activation of the caspases.
Stennicke
H R
HR
The Program for Apoptosis and Cell Death, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Salvesen
G S
GS
D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism*; D053804:Granzymes; D006801:Humans; D011487:Protein Conformation; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
D004792:Enzyme Precursors; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; D020169:Caspases