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蛋白质翻译后修饰在生物节律调控中的作用机制研究进展

赵子迪¹, 胡琦淼¹, 杨梓艺², 孙鹏程¹, 荆博文³, 满容汐¹, 许愿⁴, 闫如玉⁵, 瞿思遥⁶, 裴建飞^6,*

¹中国医科大学第二临床学院，沈阳 110122；²中国医科大学口腔医学院，沈阳 110122；³中国医科大学基础医学院，沈阳 110122；⁴中国医科大学第四临床学院，沈阳 110122；⁵中国医科大学中英联合学院，沈阳 110122；⁶中国医科大学生命科学学院，沈阳 110122

摘要

生物钟在生命体的基因表达、代谢调控、免疫反应和睡眠-觉醒周期等多种生理过程中发挥重要作用。蛋白质翻译后修饰(post-translational modifications, PTMs)是维持生物钟精确振荡的重要调控机制，通过调节核心时钟蛋白的稳定性、活性、细胞定位和蛋白-蛋白相互作用等，使核心时钟蛋白能够及时响应环境和细胞内的变化，从而维持生物钟调节的周期性振荡。不同类型的PTMs通过各自的分子机制共同维持生物钟的正常运转。为了更深入理解这些修饰在生物钟调控中的具体机制及其功能，本文综述了磷酸化、乙酰化、泛素化、SUMO化和氧化修饰等主要PTMs类型，重点探讨它们对核心时钟蛋白及其所在通路中的作用，以期进一步明晰生物钟的分子调控机制，并为生物钟紊乱相关疾病的治疗提供理论基础。

关键词： 蛋白质翻译后修饰; 生物钟; 核心时钟蛋白

Advances in the role of protein post-translational modifications in circadian rhythm regulation

ZHAO Zi-Di¹, HU Qi-Miao¹, YANG Zi-Yi², SUN Peng-Cheng¹, JING Bo-Wen³, MAN Rong-Xi¹, XU Yuan⁴, YAN Ru-Yu⁵, QU Si-Yao⁶, PEI Jian-Fei^6,*

¹The Second Clinical College, China Medical University, Shenyang 110122, China；²School and Hospital of Stomatology, China Medical University, Shenyang 110122, China；³College of Basic Medical School, China Medical University, Shenyang 110122, China；⁴The Fourth Clinical College, China Medical University, Shenyang 110122, China；⁵The Queen's University of Belfast Joint College, China Medical University, Shenyang 110122, China；⁶College of Life Sciences, China Medical University, Shenyang 110122, China

Abstract

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.

Key words: post-translational modifications; circadian clock; core clock protein

收稿日期：　　录用日期：

通讯作者：裴建飞　　E-mail:

DOI: 10.13294/j.aps.2024.0092

引用本文：

赵子迪, 胡琦淼, 杨梓艺, 孙鹏程, 荆博文, 满容汐, 许愿, 闫如玉, 瞿思遥, 裴建飞. 蛋白质翻译后修饰在生物节律调控中的作用机制研究进展[J]. 生理学报 2025; 77 (4): 605-626.

ZHAO Zi-Di, HU Qi-Miao, YANG Zi-Yi, SUN Peng-Cheng, JING Bo-Wen, MAN Rong-Xi, XU Yuan, YAN Ru-Yu, QU Si-Yao, PEI Jian-Fei. Advances in the role of protein post-translational modifications in circadian rhythm regulation. Acta Physiol Sin 2025; 77 (4): 605-626 (in Chinese with English abstract).