Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis.
10.1007/s13238-011-1071-9
- Author:
Xiao-Xi GUO
1
;
Hanna KIM
;
Yang LI
;
Hyungshin YIM
;
Seung Ki LEE
;
Ying-Hua JIN
Author Information
1. Key Laboratory for Molecular Enzymology & Engineering of the Ministry of Education, Jilin University, Changchun 130012, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents, Phytogenic;
pharmacokinetics;
pharmacology;
Apoptosis;
drug effects;
Cell Cycle;
Cyclin-Dependent Kinase 2;
metabolism;
HeLa Cells;
Humans;
Mitochondria;
metabolism;
Paclitaxel;
pharmacokinetics;
pharmacology;
Permeability;
Up-Regulation
- From:
Protein & Cell
2011;2(7):543-553
- CountryChina
- Language:English
-
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.
