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[昼夜节律钟功能的分子机制]

[Molecular mechanisms of circadian clock functioning].

作者信息

Karbovskyĭ L L, Minchenko D O, Garmash Ia A, Minchenko O G

出版信息

Ukr Biokhim Zh (1999). 2011 May-Jun;83(3):5-24.

Abstract

Most physiological processes of all organisms are rhythmic with a period of about 24 h and are generated by an endogenous biological CLOCK present in all cells. However, there is also a central CLOCK--the primary circadian pacemaker which is localized in the suprachiasmatic nuclei of the mammalian hypothalamus. Factors of groups Period (PER1, PER2 and PER3), BMAL (BMAL1 and BMAL2), CRYptochromes (CRY1 and CRY2) as well as some other factors are the components of this circadian CLOCK system. Some of these genes contain E-box sequences and their expression is regulated by a transcription factor complex CLOCK-BMAL1. The enzymes responsible for the post-translational modification of circadian gene products are also the components of circadian CLOCK system. These enzymes define CLOCK's work and determine the duration of circadian biorhythm and functional state of the whole organism. The most important of these enzymes are casein kinase-1epsilon and -1delta. We have analysed data about the interconnection between the circadian CLOCK system, cell cycle, and cancerogenesis as well as about the sensitivity of circadian gene expression to the action of toxic agents and nanomaterials.

摘要

所有生物体的大多数生理过程都具有约24小时的节律,并且由存在于所有细胞中的内源性生物钟产生。然而,也存在一个中央生物钟——主要的昼夜节律起搏器,它位于哺乳动物下丘脑的视交叉上核中。周期蛋白(PER1、PER2和PER3)、BMAL(BMAL1和BMAL2)、隐花色素(CRY1和CRY2)以及其他一些因子是这个昼夜节律生物钟系统的组成部分。这些基因中的一些含有E-box序列,它们的表达受转录因子复合物CLOCK-BMAL1调控。负责昼夜节律基因产物翻译后修饰的酶也是昼夜节律生物钟系统的组成部分。这些酶决定了生物钟的工作,并决定了昼夜生物节律的持续时间和整个生物体的功能状态。其中最重要的酶是酪蛋白激酶-1ε和-1δ。我们分析了有关昼夜节律生物钟系统、细胞周期和癌症发生之间的相互联系的数据,以及昼夜节律基因表达对有毒物质和纳米材料作用的敏感性的数据。

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