Human INT6 interacts with MCM7 and regulates its stability during Sphase of the cell cycle

被引：17

作者：

Buchsbaum, S. ^{[1
]}

Morris, C. ^{[1
]}

Bochard, V. ^{[1
]}

Jalinot, P. ^{[1
]}

机构：

[1] Ecole Normale Super Lyon, CNRS, Lab Biol Mol Cellule, UMR 5161,IFR 128 Biosci Lyon Gerland, F-69364 Lyon 07, France

来源：

ONCOGENE | 2007年 / 26卷 / 35期

关键词：

INT6; MCM7; polyubiquitylation; protein degradation; DNA replication;

D O I：

10.1038/sj.onc.1210314

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 mouse int6 gene is a frequent integration site of the mouse mammary tumor virus and INT6 silencing by RNA interference in HeLa cells causes an increased number of cells in the G2/M phases of the cell cycle, along with mitotic defects. In this report, we investigated the functional significance of the interaction between INT6 and MCM7, which was observed in a two-hybrid screen performed with INT6 as bait. It was found that proteasome inhibition strengthens interaction between both proteins and that INT6 stabilizes MCM7. Removal of MCM7 from chromatin as replication proceeds was accelerated in INT6-silenced cells and reduced amounts of protein were transiently observed, followed by a correction resulting from stimulation of mcm7 gene expression. Synchronized cells depleted for either INT6 or MCM7 display a reduction in thymidine incorporation and a reinforced association of RPA and claspin with chromatin. These data show that INT6 stabilizes chromatin-bound MCM7 and that alteration of this effect is associated with replication deficency.

引用

页码：5132 / 5144

页数：13

共 41 条

[1] Fission yeast homolog of murine int-6 protein, encoded by mouse mammary tumor virus integration site, is associated with the conserved core subunits of eukaryotic translation initiation factor 3 [J].