Genotoxic-activated G2-M checkpoint exit is dependent on CDC25B phosphatase expression.
Mol Cancer Ther
; 5(6): 1446-51, 2006 Jun.
Article
en En
| MEDLINE
| ID: mdl-16818502
ABSTRACT
Cell cycle arrest at the G2-M checkpoint is an essential feature of the mechanisms that preserve genomic integrity. CDC25 phosphatases control cell cycle progression by dephosphorylating and activating cyclin-dependent kinase/cyclin complexes. Their activities are, therefore, tightly regulated to modulate cell cycle arrest in response to DNA damage exposure. Here, we report that overexpression of CDC25B affects viability, reduces clonogenic efficiency, and increases sensitivity of cancer cells to a genotoxic agent. We show that ectopic expression of CDC25B results in bypass of a genotoxic-induced G2-M checkpoint. In addition, cancer cells constitutively expressing high level of CDC25B are shown to be prone to exit prematurely from the G2-M checkpoint arrest and to enter mitosis. Finally, we show that this exit is dependent on CDC25B expression. Together with previous results, our data strongly support a model in which CDC25B is the key phosphatase that controls entry into mitosis after DNA damage, thus emphasizing the relevance of its overexpression in many human tumors.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Ciclo Celular
/
Fosfatasas cdc25
Límite:
Humans
Idioma:
En
Revista:
Mol Cancer Ther
Asunto de la revista:
ANTINEOPLASICOS
Año:
2006
Tipo del documento:
Article
País de afiliación:
Francia