Genotoxic-activated G2-M checkpoint exit is dependent on CDC25B phosphatase expression

被引:47
作者
Bugler, Beatrix
Quaranta, Muriel
Aressy, Bernadette
Brezak, Marie-Christine
Prevost, Gregoire
Ducommun, Bernard
机构
[1] Univ Toulouse 3, Lab Biol Cellulaire & Mol Controle Proliferat, CNRS, UMR 5088,IFR 109,Inst Explorat Fonct Genome, F-31062 Toulouse, France
[2] Inst Henri Beaufour, IPSEN, F-91952 Les Ulis, France
关键词
D O I
10.1158/1535-7163.MCT-06-0099
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cell cycle arrest at the G(2)-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 G(2)-M checkpoint. In addition, cancer cells constitutively expressing high level of CDC25B are shown to be prone to exit prematurely from the G(2)-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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收藏
页码:1446 / 1451
页数:6
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