The circadian gene Per1 plays an important role in cell growth and DNA damage control in human cancer cells

被引：513

作者：

Gery, S ^{[1
]}

Komatsu, N ^{[1
]}

Baldjyan, L ^{[1
]}

Yu, A ^{[1
]}

Koo, D ^{[1
]}

Koeffler, HP ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Div Hematol Oncol, Los Angeles, CA 90048 USA

来源：

MOLECULAR CELL | 2006年 / 22卷 / 03期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.molcel.2006.03.038

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 Per1 gene is a core clock factor that plays an essential role in generating circadian rhythms. Recent data reveal that major biological pathways, including those critical to cell division, are under circadian control. We report here that Per1 provides an important link between the circadian system and the cell cycle system. Overexpression of Per1 sensitized human cancer cells to DNA damage-induced apoptosis; in contrast, inhibition of Per1 in similarly treated cells blunted apoptosis. The apoptotic phenotype was associated with altered expression of key cell cycle regulators. In addition, Per1 interacted with the checkpoint proteins ATM and Chk2. Ectopic expression of Per1 in human cancer cell lines led to significant growth reduction. Finally, Pert levels were reduced in human cancer patient samples. Our results highlight the importance of circadian regulation to fundamental cellular functions and support the hypothesis that disruption of core clock genes may lead to cancer development.

引用

页码：375 / 382

页数：8

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