The circadian gene Per1 plays an important role in cell growth and DNA damage control in human cancer cells
The circadian gene Per1 plays an important role in cell growth and DNA damage control in human cancer cells
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DOI：
10.1016/j.molcel.2006.03.038
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发表时间：
2006-05-05
期刊：
影响因子：
16
通讯作者：
Koeffler, HP
中科院分区：
文献类型：
--
作者：
Gery, S;Komatsu, N;Koeffler, HP
Per 1基因是一个核心时钟因子，在产生昼夜节律中起着至关重要的作用。最近的数据显示，主要的生物学途径，包括那些对细胞分裂至关重要的途径，都受到昼夜节律的控制。我们在这里报告，Per 1提供了一个重要的昼夜节律系统和细胞周期系统之间的联系。Per 1的过表达使人癌细胞对DNA损伤诱导的凋亡敏感;相反，在类似处理的细胞中抑制Per 1使凋亡钝化。凋亡表型与关键细胞周期调节因子的表达改变相关。此外，Per 1与检查点蛋白ATM和Chk 2相互作用。Per 1在人癌细胞系中的异位表达导致显著的生长减少。最后，Pert水平在人类癌症患者样品中降低。我们的研究结果强调了昼夜节律调节对基本细胞功能的重要性，并支持核心时钟基因的破坏可能导致癌症发展的假设。
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.