Okamoto-Uchida Yoshimi, Izawa Junko, Nishimura Akari, Hattori Atsuhiko, Suzuki Nobuo, Hirayama Jun
Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan.
Department of Clinical Engineering, Faculty of Health Sciences, Komatsu University, 10-10 Doihara-machi, Komatsu, Ishikawa, 923-0921, Japan.
Curr Genomics. 2019 Aug;20(5):332-339. doi: 10.2174/1389202919666191014094349.
Circadian clocks are intrinsic, time-tracking systems that bestow upon organisms a survival advantage. Under natural conditions, organisms are trained to follow a 24-h cycle under environmental time cues such as light to maximize their physiological efficiency. The exact timing of this rhythm is established cell-autonomous oscillators called cellular clocks, which are controlled by transcription/translation-based negative feedback loops. Studies using cell-based systems and genetic techniques have identified the molecular mechanisms that establish and maintain cellular clocks. One such mechanism, known as post-translational modification, regulates several aspects of these cellular clock components, including their stability, subcellular localization, transcriptional activity, and interaction with other proteins and signaling pathways. In addition, these mechanisms contribute to the integration of external signals into the cellular clock machinery. Here, we describe the post-translational modifications of cellular clock regulators that regulate circadian clocks in vertebrates.
昼夜节律时钟是内在的时间追踪系统,赋予生物体生存优势。在自然条件下,生物体通过诸如光等环境时间线索接受训练,遵循24小时周期,以最大限度地提高其生理效率。这种节律的确切时间是由称为细胞时钟的细胞自主振荡器建立的,细胞时钟由基于转录/翻译的负反馈回路控制。使用基于细胞的系统和基因技术的研究已经确定了建立和维持细胞时钟的分子机制。一种这样的机制,称为翻译后修饰,调节这些细胞时钟组件的几个方面,包括它们的稳定性、亚细胞定位、转录活性以及与其他蛋白质和信号通路的相互作用。此外,这些机制有助于将外部信号整合到细胞时钟机制中。在这里,我们描述了调节脊椎动物昼夜节律时钟的细胞时钟调节因子的翻译后修饰。