CASPASE-DEPENDENT ACTIVATION OF CYCLIN-DEPENDENT KINASES DURING FAS-INDUCED APOPTOSIS IN JURKAT CELLS

The activation of cyclin-dependent kinases (cdks) has been implicated in apoptosis induced by various stimuli. We find that the Fas-induced activation of cdc2 and cdk2 in Jurkat cells is not dependent on protei n synthesis, which is shut down very early during apoptosis before cas pase-3 activation. Instead, activation of these kinases seems to resul t from both a rapid cleavage of Wee1 (an inhibitory kinase of cdc2 and cdk2) and inactivation of anaphase-promoting complex (the specific sy stem for cyclin degradation), in which CDC27 homolog is cleaved during apoptosis. Both Wee1 and CDC27 are shown to be substrates of the casp ase-3-like protease. Although cdk activities are elevated during Fas-i nduced apoptosis in Jurkat cells, general activation of the mitotic pr ocesses does not occur. Our results do not support the idea that apopt osis is simply an aberrant mitosis but, instead, suggest that a subset of mitotic mechanisms plays an important role in apoptosis through el evated cdk activities.