Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis
Protein & Cell
;
(12): 543-553, 2011.
Article
in English
| WPRIM
| ID: wpr-757067
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Permeability
/
Pharmacology
/
Pharmacokinetics
/
HeLa Cells
/
Cell Cycle
/
Up-Regulation
/
Paclitaxel
/
Apoptosis
/
Cyclin-Dependent Kinase 2
/
Metabolism
Limits:
Humans
Language:
English
Journal:
Protein & Cell
Year:
2011
Type:
Article
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