Interacting molecular loops in the mammalian circadian clock
Interacting molecular loops in the mammalian circadian clock
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DOI：
10.1126/science.288.5468.1013
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发表时间：
2000-05-12
期刊：
影响因子：
56.9
通讯作者：
Reppert, SM
中科院分区：
文献类型：
--
作者：
Shearman, LP;Sriram, S;Reppert, SM
我们发现，在小鼠中，主生物钟的核心机制包括相互作用的正、负转录和翻译反馈环。对时钟/时钟突变小鼠、纯合子周期2(Brdm1)突变小鼠和隐色素缺陷小鼠的分析显示，小节律发生了实质性变化，这与周期2在BMal1环的正向调节中的主导作用一致。体外分析隐色素对CLOCK：BMal1介导的转录的抑制作用表明，这种抑制是通过直接的蛋白质：蛋白质的相互作用，不依赖于周期和永恒的蛋白质。PERIO2是BMal1环的正调节因子，而隐花色素是周期和隐花色素循环的负调节因子。
We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback Loops. Analysis of Clock/Clock mutant mice, homozygous period2(Brdm1) mutants, and Cryptochrome-deficient mice reveals substantially altered Small rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal1 Loop. In vitro analysis of CRYPTOCHROME inhibition of CLOCK: BMAL1-mediated transcription shows that the inhibition is through direct protein:protein interactions, independent of the PERIOD and TIMELESS proteins. PERIOD2 is a positive regulator of the Bmal1 Loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles.