A link between cell cycle and cell death: Bax and Bcl-2 modulate Cdk2 activation during thymocyte apoptosis

Resting thymocytes undergoing apoptosis in response to specific stimuli deg rade the cdk inhibitor p27(Kip1) and upregulate Cdk2 kinase activity. Inhib ition of Cdk2 kinase activity efficiently blocks cell death via certain apo ptosis pathways whereas overexpression of Cdk2 accelerates such cell death, suggesting its involvement in the signal transduction pathways activated b y certain apoptotic stimuli. We found that Cdk2 activation during thymocyte apoptosis can be regulated by p53, Bar and Bcl-2. The highly elevated Cdk2 kinase activity in the apoptosing thymocytes is not associated with its ca nonical cyclins, cyclin E and cyclin A, and requires de novo synthesis of p roteins for activation to take place. We therefore propose Cdk2 activation to be a crucial event in distinct pathways of apoptosis and the point at wh ich the cell cycle and cell death pathways interact.