Mueller Toni, Ouyang Xiaosen, Johnson Michelle S, Qian Wei-Jun, Chatham John C, Darley-Usmar Victor, Zhang Jianhua
Department of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, United States.
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States.
Front Aging. 2021 Mar 12;1:620382. doi: 10.3389/fragi.2020.620382. eCollection 2020.
O-GlcNAcylation is a protein posttranslational modification that results in the addition of O-GlcNAc to Ser/Thr residues. Since its discovery in the 1980s, it has been shown to play an important role in a broad range of cellular functions by modifying nuclear, cytosolic, and mitochondrial proteins. The addition of O-GlcNAc is catalyzed by O-GlcNAc transferase (OGT), and its removal is catalyzed by O-GlcNAcase (OGA). Levels of protein O-GlcNAcylation change in response to nutrient availability and metabolic, oxidative, and proteotoxic stress. OGT and OGA levels, activity, and target engagement are also regulated. Together, this results in adaptive and, on occasions, detrimental responses that affect cellular function and survival, which impact a broad range of pathologies and aging. Over the past several decades, approaches and tools to aid the investigation of the regulation and consequences of protein O-GlcNAcylation have been developed and enhanced. This review is divided into two sections: 1) We will first focus on current standard and advanced technical approaches for assessing enzymatic activities of OGT and OGT, assessing the global and specific protein O-GlcNAcylation and 2) we will summarize findings of functional consequences of changing protein O-GlcNAcylation, using genetic and pharmacological approaches.
O-连接的N-乙酰葡糖胺化（O-GlcNAcylation）是一种蛋白质翻译后修饰，其结果是在丝氨酸/苏氨酸残基上添加O-GlcNAc。自20世纪80年代被发现以来，已表明它通过修饰核蛋白、胞质蛋白和线粒体蛋白在广泛的细胞功能中发挥重要作用。O-GlcNAc的添加由O-GlcNAc转移酶（OGT）催化，其去除由O-GlcNAcase（OGA）催化。蛋白质O-GlcNAcylation的水平会根据营养物质的可利用性以及代谢、氧化和蛋白毒性应激而发生变化。OGT和OGA的水平、活性及靶点结合也受到调控。这些共同导致了影响细胞功能和存活的适应性反应，有时还会产生有害反应，进而影响广泛的病理状况和衰老过程。在过去几十年里，有助于研究蛋白质O-GlcNAcylation调控及其后果的方法和工具不断得到开发和改进。本综述分为两个部分：1）我们将首先聚焦于评估OGT和OGA酶活性、评估整体及特定蛋白质O-GlcNAcylation的当前标准技术和先进技术方法；2）我们将总结利用遗传学和药理学方法改变蛋白质O-GlcNAcylation所产生的功能后果的研究发现。
