摘要
生物体的睡眠/觉醒、进食等行为以及各种生理、生化、代谢过程都遵循着大约24 h的周期性变化,称为昼夜节律(circadian rhythms)。昼夜节律与能量代谢之间存在着紧密的联系。位于下丘脑视交叉上核(suprachiasmatic nuclei,SCN)的中枢生物钟与外周组织细胞中的生物钟共同组成了哺乳动物的昼夜节律系统。以CLOCK/BMAL1异二聚体为核心的转录/翻译负反馈环保障了节律系统的正常运行。各种蛋白质翻译后修饰参与了昼夜节律的调控。综述了氧连β-N-乙酰葡糖胺修饰(O-Glc NAcylation)在调节昼夜节律中发挥的重要作用。O-Glc NAc修饰可以增强一些生物钟蛋白的稳定性及转录活性,也可以影响其他一些生物钟蛋白的磷酸化及细胞定位。抑制生物钟蛋白的O-Glc NAc修饰导致细胞节律衰弱和多种节律基因表达下调。研究表明,O-Glc NAc作为机体能量代谢的感受器参与了多条细胞代谢相关信号转导通路的调节,O-Glc NAc修饰为能量代谢影响昼夜节律提供了一条新的途径。
Various physiological, biochemical and metabolic processes and behaviors show a circadian rhythm of about 24 hours. There is a close relationship between circadian rhythms and metabolism. In mammals, the circadian system is organized in a highly hierarchical architecture, composed of a central pacemaker in the brain＇s suprachiasmatic nuclei（SCN） and subsidiary clocks in peripheral organs. Transcription/translation negative feedback loops involving CLOCK/BMAL1 heterodimer are considered as the prime molecular mechanism sustaining intracellular rhythms. Post-translational modifications play important roles in regulating circadian core proteins. Here, we review that core clock proteins are modified with an O-linked β-N-acetylglucosamine（O-Glc NAc）. O-Glc NAcylation of clock proteins may modulate the stabilities, transcriptional activities, phosphorylation and cellular location. Conversely, inhibition of O-Glc NAcylation results in damped circadian rhythms of clock gene expression. As O-Glc NAcylation is sensitive to the glucose level, such modification may provide a new mechanism linking metabolism to circadian rhythms.
出处
《生命科学》
CSCD
2015年第11期1403-1408,共6页
Chinese Bulletin of Life Sciences
基金
国家自然科学基金项目(31371187)
高等学校博士学科点专项科研基金(博导类
20110162110035)
