Human Cdc25 A inactivation in response to S phase inhibition and its role in preventing premature mitosis

被引：174

作者：

Molinari, M ^{[1
]}

Mercurio, C ^{[1
]}

Dominguez, J ^{[1
]}

Goubin, F ^{[1
]}

Draetta, GF ^{[1
]}

机构：

[1] European Inst Oncol, I-20141 Milan, Italy

来源：

EMBO REPORTS | 2000年 / 1卷 / 01期

关键词：

D O I：

10.1093/embo-reports/kvd018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Cdc25 A phosphatase is required for the G(1)-S transition of the cell cycle and is overexpressed in human cancers. We found that it is ubiquitylated and rapidly degraded by the proteasome and that its levels increase from G(1) until mitosis. By treating cells with the DNA synthesis inhibitor hydroxyurea, Cdc25 A rapidly decreased in abundance, and this was accompanied by an increase-in Cdk2 phosphotyrosine content and a decrease in Cdk2 kinase activity. Cdc25 A overexpression altered the ability of cells to arrest in the presence of hydroxyurea, and caused them to undergo premature chromosome condensation. Cdc25 A overexpression could render tumor cells less sensitive to DNA replication checkpoints, thereby contributing to their genomic instability.

引用

页码：71 / 79

页数：9

共 41 条

[1] Phosphorylation of human CDC25B phosphatase by CDK1-cyclin A triggers its proteasome-dependent degradation [J].