蛋白质亚磺酰化修饰及其在生理和病理过程中的作用  

The Roles of Protein Sulfenylation in Physiological and Pathological Processes

作　　者：高琪 王淑珍[1] GAO Qi;WANG Shu-Zhen(School of Life Science and Technology,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学生命科学与技术学院,南京211198

出　　处：《中国生物化学与分子生物学报》2023年第2期196-203,共8页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家科技重大专项(No.2018ZX09201002-001-001)资助。

摘　　要：细胞正常生理或病理过程中均伴随着活性氧(ROS)和活性氮(RNS)的产生,引起蛋白质半胱氨酸发生氧化翻译后修饰。亚磺酰化是氧化翻译后修饰中的一种,指ROS将蛋白质的巯基氧化成亚磺酰基(R-SOH)的过程,广泛存在于多种物种中。亚磺酰化修饰蛋白质的捕获、富集和修饰位点的确定目前仍极具挑战性。半胱氨酸亚磺酰化的检测方法主要包括基于转录因子Yap1和基于小分子化合物dimedone或bicyclo[6.1.0]nonyne的分子探针。在此基础上,研究人员通过偶联生物素等标签分子又设计出了更多便于富集亚磺酰化蛋白质的衍生物探针。将亚磺酰化蛋白质捕获和富集后,与LC-MS/MS等质谱分析技术联用,则可确定发生亚磺酰化修饰的半胱氨酸位点。近几年的研究表明,细胞信号通路中的许多蛋白质或酶都会发生亚磺酰化修饰,调控蛋白质功能、稳定性或催化活性,从而引起下游信号通路或代谢过程的变化,进而影响机体生理或病理状态。随着对蛋白质亚磺酰化修饰的深入研究,越来越多疾病的发生发展新机制被发现,靶向该修饰有望为疾病治疗提供新的策略。本文从蛋白质氧化修饰的过程和亚磺酰化修饰检测的方法入手进行阐述,总结了近几年亚磺酰化修饰在生理与病理过程中的研究进展和在癌症治疗中的应用。The cellular physiological and pathological processes are often accompanied by the production of reactive oxygen species(ROS) and reactive nitrogen species(RNS),which can initiate oxidative post-translational modifications on the thiol groups(-SH) of cysteines in proteins.Sulfenylation,the process that ROS oxidizes the thiol group of proteins to sulfenylation(R-SOH),is one type of the oxidative post-translational modifications existing widely in different species.The capture and enrichment of sulfenylated proteins and identification of the sulfenylation sites are challenging in the present research of protein sulfenylation.Based on the transcription factor Yap1 and small molecular chemicals,probes were developed such as dimedone and bicyclo[6.1.0]nonyne,and they were used to directly detect the sulfenylation of proteins.By coupling biotin or other labeling molecules,more new and efficient derivative probes were developed to enrich sulfenylated proteins.After capturing and enriching for the sulfenylated proteins,the sulfenylated cysteine sites can be determined by mass spectrometry techniques such as LC-MS/MS analysis.Recently,studies have shown that lots of proteins in cellular signaling pathways or kinases can undergo sulfenylation modification to regulate their function,stability or catalytic activity,so as to cause changes in downstream signaling pathways or metabolic processes,and then affect the physiological or pathological state of the organism.With the in-depth study of protein sulfenylation modification,more and more novel pathogenesis of diseases have been revealed,suggesting targeting protein sulfenylation might provide a new strategy for disease therapy.This article reviews the recent research progresses in the molecular process and detection method of sulfenylation,and roles of sulfenylation in the physiological and pathological processes,and the application of sulfenylation in cancer treatment.

关 键 词：翻译后修饰 氧化应激 活性氧 亚磺酰化修饰 

分 类 号：Q5[生物学—生物化学] Q7