昼夜节律基因Period2在体内肿瘤抑制和DNA损伤反应中起重要作用。

The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo.

作者信息

Fu Loning, Pelicano Helene, Liu Jinsong, Huang Peng, Lee Cheng

机构信息

Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

出版信息

Cell. 2002 Oct 4;111(1):41-50. doi: 10.1016/s0092-8674(02)00961-3.

DOI:10.1016/s0092-8674(02)00961-3

PMID:12372299

Abstract

The Period2 gene plays a key role in controlling circadian rhythm in mice. We report here that mice deficient in the mPer2 gene are cancer prone. After gamma radiation, these mice show a marked increase in tumor development and reduced apoptosis in thymocytes. The core circadian genes are induced by gamma radiation in wild-type mice but not in mPer2 mutant mice. Temporal expression of genes involved in cell cycle regulation and tumor suppression, such as Cyclin D1, Cyclin A, Mdm-2, and Gadd45alpha, is deregulated in mPer2 mutant mice. In particular, the transcription of c-myc is controlled directly by circadian regulators and is deregulated in the mPer2 mutant. Our studies suggest that the mPer2 gene functions in tumor suppression by regulating DNA damage-responsive pathways.

摘要

Period2基因在控制小鼠昼夜节律中起关键作用。我们在此报告，mPer2基因缺陷的小鼠易患癌症。γ射线辐射后，这些小鼠的肿瘤发生显著增加，胸腺细胞凋亡减少。野生型小鼠经γ射线辐射后核心昼夜节律基因被诱导表达，但mPer2突变小鼠中则不然。细胞周期调控和肿瘤抑制相关基因，如细胞周期蛋白D1、细胞周期蛋白A、Mdm-2和Gadd45α的时序表达在mPer2突变小鼠中失调。特别是，c-myc的转录直接受昼夜节律调节因子控制，在mPer2突变体中失调。我们的研究表明，mPer2基因通过调节DNA损伤反应途径发挥肿瘤抑制作用。