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. 2011 Aug 6;2(7):543–553. doi: 10.1007/s13238-011-1071-9

Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis

Xiao-Xi Guo 1, Hanna Kim 2, Yang Li 1, Hyungshin Yim 2, Seung Ki Lee 2,✉, Ying-Hua Jin 1,✉
PMCID: PMC4875236  PMID: 21822799

Abstract

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 paclitaxel-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.

Keywords: apoptosis, cyclin-dependent kinase 2, cytochrome c release, mitochondrial membrane potential, paclitaxel

Contributor Information

Seung Ki Lee, Email: sklcrs@plaza.snu.ac.kr.

Ying-Hua Jin, Email: yhjin@jlu.edu.cn.

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