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 protein synthesis, which is shut down very early during apoptosis before caspase-3 activation. Instead, activation of these kinases seems to result from both a rapid cleavage of Wee1 (an inhibitory kinase of cdc2 and cdk2) and inactivation of anaphase-promoting complex (the specific system for cyclin degradation), in which CDC27 homolog is cleaved during apoptosis. Both Wee1 and CDC27 are shown to be substrates of the caspase-3-like protease. Although cdk activities are elevated during Fas-induced apoptosis in Jurkat cells, general activation of the mitotic processes does not occur. Our results do not support the idea that apoptosis is simply an aberrant mitosis but, instead, suggest that a subset of mitotic mechanisms plays an important role in apoptosis through elevated cdk activities.
Zhou
B B
BB
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Li
H
H
Yuan
J
J
Kirschner
M W
MW
D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D017209:Apoptosis / Q000502:physiology*; D016203:CDC2 Protein Kinase / Q000502:physiology*; D042846:CDC2-CDC28 Kinases; D053148:Caspase 3; D020169:Caspases; D018797:Cell Cycle Proteins / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D019169:Jurkat Cells; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000502:physiology*
D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; C577366:CDC27 protein, human; D018797:Cell Cycle Proteins; D019014:fas Receptor; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases