Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis
Protein & Cell
;
(12): 543-553, 2011.
Artigo
em Inglês
| 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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Permeabilidade
/
Farmacologia
/
Farmacocinética
/
Células HeLa
/
Ciclo Celular
/
Regulação para Cima
/
Paclitaxel
/
Apoptose
/
Quinase 2 Dependente de Ciclina
/
Metabolismo
Limite:
Humanos
Idioma:
Inglês
Revista:
Protein & Cell
Ano de publicação:
2011
Tipo de documento:
Artigo
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