How is Caspase-2 Activated?
Before addressing the function of caspase-2, it is worthwhile to consider the existing data regarding the activation mechanism of caspase-2. When caspase-2 was identified there was one known mechanism of activation for caspases, sequential cleavage of the zymogen to release the large and small peptides that assembled to form the active heterotetramer. This mode of activation was assumed to hold for other caspases, and cleavage of caspase-2 was used as an indication of activation. Thus, much of the data showing a role for caspase-2 in a particular death paradigm relied on showing cleavage of caspase-2. Over the ensuing years, with the identification of at least 13 mammalian caspases, it has become clear that there are several ways of activating caspases. In addition to cleavage, these include oligomerization and formation of an apoptosome.16,17,18,19 It is not clear yet as to which mechanism leads to activation of caspase-2. Identification of an adaptor protein for caspase-2, RAIDD, sug
