The cyclin-dependent kinase Cdk2 regulates thymocyte apoptosis

Aberrant activation of cell cycle molecules has been postulated to play a r ole in apoptosis ("catastrophic cell. cycle"). Here we show that in noncycl ing developing thymocytes, the cyclin-dependent kinase Cdk2 is activated in response to all specific and nonspecific apoptotic stimuli tested, includi ng peptide-specific thymocyte apoptosis. Cdk2 was found to function upstrea m of the tumor suppressor p53, transactivation of the death promoter Bar, a lterations of mitochondrial permeability, Bcl-2, caspase activation, and ca spase-dependent proteolytic cleavage of the retinoblastoma protein. Inhibit ion of Cdk2 completely protected thymocytes from apoptosis, mitochondrial c hanges, and caspase activation. These data provide the first evidence that Cdk2 activity is crucial for the induction of thymocyte apoptosis.