Light-independent role of CRY1 and CRY2 in the mammalian circadian clock
Light-independent role of CRY1 and CRY2 in the mammalian circadian clock
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DOI：
10.1126/science.286.5440.768
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发表时间：
1999-10-22
期刊：
影响因子：
56.9
通讯作者：
Weitz, CJ
中科院分区：
文献类型：
--
作者：
Griffin, EA;Staknis, D;Weitz, CJ
隐花色素（CRY）是果蝇生物钟的感光细胞，它以光依赖的方式与生物钟的组成部分TIM结合并阻断其功能。在哺乳动物中，遗传学证据表明生物钟中的一个角色，与假设的感光功能不同。研究表明，哺乳动物CRY 1和CRY 2可作为驱动Per 1转录的激活因子CLOCK-BMAL 1的光非依赖性抑制剂。CLOCK 1或CLOCK 2（或两者）与CLOCK和BMAL 1以及PER 1、PER 2和TIM显示出光依赖性相互作用。因此，哺乳动物的神经元作为光不依赖性的昼夜节律钟的组成部分，并可能通过接触激活剂及其反馈抑制剂来调节Per 1转录循环。
Cryptochrome (CRY), a photoreceptor for the circadian clock in Drosophila, binds to the clock component TIM in a light-dependent fashion and blocks its function. In mammals, genetic evidence suggests a role for CRYs within the clock, distinct from hypothetical photoreceptor functions. Mammalian CRY1 and CRY2 are here shown to act as light-independent inhibitors of CLOCK-BMAL1, the activator driving Per1 transcription. CRY1 or CRY2 (or both) showed Light-independent interactions with CLOCK and BMAL1, as well as with PER1, PER2, and TIM. Thus, mammalian CRYs act as light-independent components of the circadian clock and probably regulate Per1 transcriptional cycling by contacting both the activator and its feedback inhibitors.