title: Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis.
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, p21( WAF1/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.
authors.affiliation: Key Laboratory for Molecular Enzymology & Engineering of the Ministry of Education, Jilin University, Changchun 130012, China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Guo
authors.forename: Hanna
authors.initials: H
authors.lastname: Kim
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Hyungshin
authors.initials: H
authors.lastname: Yim
authors.forename: Seung Ki
authors.initials: SK
authors.lastname: Lee
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Jin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology*; D010539:Permeability; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D017239:Paclitaxel