Sequential activation of cyclin-dependent kinases (Cdks)controls mammalian cell cycle.Here we demonstrate that the upregulation of cyclin-dependent kinase 2 (Cdk2)activity coincides with the loss of mitochondrial membrane potential (MMP) in pac1litaxel-induced apoptosis.Ectopic expression of the dominant negative Cdk2 (Cdk2-dn) and a specific Cdk2 inhibitor,p21WAF1/CIP1,effectively suppresses the loss of MMP,the release of cytochrome c,and subsequent activation of caspase-3 in paclitaxel-treated cells.Whereas forced activation of Cdk2 by overexpression of cyclin A dramatically promotes these events.We further show that Cdk2 activation status does not interfere with a procedure that lies downstream of cytochrome c release induced by Bax protein.These findings suggest that Cdk2 kinase can regulate apoptosis at earlier stages than mitochondrial permeability transition and cytochrome c release.