Apoptosis is mainly brought about by the activation of caspases, a protease family with unique substrate selectivity. In mammals, different complexes like the DISC complex or the apoptosome complexes have been delineated leading to the cleavage and thus activation of the executioner caspases. Although @entity185 is the main executioner caspase in apoptosis induced by serum starvation in AKR-2B fibroblasts as demonstrated by affinity labeling with YVK(-bio)D.aomk and partial purification of cytosolic extracts by high performance ion exchange chromatography, its activation is apparently caused by a noncanonical pathway: (1) Expression of CrmA, an inhibitor of @entity4699 , failed to suppress apoptosis; (2) There was no formation of high molecular weight complexes of @entity49302 indicative for its activation. Furthermore no cleavage of @entity7349 was observed. But surprisingly, gelfiltration experiments revealed the distribution of @entity69566 into differently sized high molecular weight complexes during apoptosis. Though the apparent molecular weights of the complexes containing @entity185 (600 kD for apoptosome and 250 kD for microapoptosome) are in accordance with recently published data, the activity profiles differ strikingly. In AKR-2B cells @entity185 is mainly recovered as uncomplexed enzyme and in much lower levels in the apoptosomes. Remarkably, the 600 kD and 250 kD complexes containing activated @entity185 were devoid of @entity49302 and cytochrome c. In addition a new 450 kD complex containing activated @entity43489 was found that is clearly separated from the @entity185 containing complexes. Furthermore, we disclose for the first time the activation of @entity35123 in response to serum starvation. Activated @entity35123 is detectable as non-complexed free enzyme in the cytosol.

Formation of noncanonical high molecular weight @entity69566 complexes and activation of XXXX during serum starvation induced apoptosis in AKR-2B mouse fibroblasts.

@entity49302 :: ('11783(Tax:10090)', 'Gene') :: ['Apaf-1'] @entity69566 :: ('12367;12368', 'Gene') :: ['caspase-3 and -6'] @entity35123 :: ('12364(Tax:10090)', 'Gene') :: ['caspase-12'] @entity185 :: ('12367(Tax:10090)', 'Gene') :: ['caspase-3'] @entity7349 :: ('12371(Tax:10090)', 'Gene') :: ['caspase-9'] @entity4699 :: ('12370(Tax:10090)', 'Gene') :: ['caspase-8'] @entity43489 :: ('12368(Tax:10090)', 'Gene') :: ['caspase-6']
@entity35123 :: (12364(Tax:10090),Gene) :: ['caspase-12']
