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Kinetic Analysis of Human -Calpain Autolysis

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The relation of autolysis to calpain activation has a long and controversial history. Early on, it was realized that calcium-induced calpain activation is accompanied by autolytic truncation of the enzyme in vitro and that sensitization to calcium occurs at the same time (1 ). The issue of the mechanistic role of autolysis in calpain activation, however, has still not been settled. Several aspects of autolysis have been addressed, such as the temporal order of autolysis and activation (2 ,3 ), the relation of autolysis to sensitization to calcium (4 ,5 ), and possible differences in the mode of autolysis between μ-and m-calpain (5 ,6 ). Much work has also been devoted to the question of the physiological relevance of calpain autolysis. Calpain action was found to be accompanied by autolysis in vivo (7 ), but opposing examples are also known (8 ). Pathological involvement of autolysis has also been suggested (9 ). The prevailing view is that autolysis is possibly a major mechanism of calpain activation, but that other mechanisms of calpain activation may also act under various conditions (10 ).
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