PDF(Pubmed)
Abstract：
PER1 is a core component of the internal time-keeping system. In the suprachiasmatic nucleus, it serves as the primary circadian pacemaker in mammalian brains. PER1 functions with other clock components to generate a feedback loop involving the transcriptional repression of gene expression to produce a circadian rhythm with an approximately 24-hour cycle. Post-transcriptional modifications (PTMs) are a basic regulatory mechanism that both perpetuate self-sustained oscillations and interpret metabolic input into circadian physiology by affecting factors such as protein stability, interactions, localization, and activity. Here we examined whether the serine/threonine protein kinase WNK3, which is expressed in a circadian rhythm, can interact and colocalize with PER1 in the SCN. In rats, WNK3 knockdown in the SCN is associated with altered sleep patterns. Moreover, WNK3 can phosphorylate PER1 to promote its degradation and is associated with circadian oscillations when PER1 is expressed in vitro.
摘要：
PER1是内部计时系统的核心组件。在视交叉上核，它是哺乳动物大脑的主要昼夜节律起搏器。PER1与其他时钟组件一起作用以产生涉及基因表达的转录抑制的反馈环,以产生具有大约24小时周期的昼夜节律。转录后修饰（PTM）是一种基本的调节机制，它既能维持自我维持的振荡，又能通过影响蛋白质稳定性等因素将代谢输入解释为昼夜节律生理学。互动,本地化,和活动。在这里，我们检查了丝氨酸/苏氨酸蛋白激酶WNK3是否以昼夜节律表达，可以与SCN中的PER1相互作用和共定位。在老鼠身上,SCN中的WNK3敲低与改变的睡眠模式相关。此外，WNK3可以磷酸化PER1以促进其降解，并且当PER1在体外表达时与昼夜节律振荡有关。
