In the mid 1980s, the identification of serine and threonine residues on nuclear and cytoplasmic proteins modified by an O-linkage by a N-acetylglucosamine moiety (O-GlcNAc) overturned the widely held assumption that glycosylation only occurred in the endoplasmic reticulum, Golgi apparatus, and secretory pathways. In contrast to traditional glycosylation, the O-GlcNAc modification does not lead to complex branched glycan structures and is rapidly cycled on and off proteins by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. Since its discovery O-GlcNAcylation has been shown to contribute to numerous cellular functions including signaling, protein localization and stability, transcription, chromatin remodeling, mitochondrial function, and cell survival. Dysregulation in O-GlcNAc cycling has been implicated in the progression of a wide range of diseases such as diabetes, diabetic complications, cancer, cardiovascular, and neurodegenerative diseases. This review will outline our current understanding of the processes involved in regulating O-GlcNAc turnover, the role of O-GlcNAcylation in regulating cellular physiology, and how dysregulation in O-GlcNAc cycling contributes to pathophysiological processes.

中文翻译：

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O-连接的 N-乙酰氨基葡萄糖 (O-GlcNAc) 蛋白修饰在细胞（病理）生理学中的作用。

在 1980 年代中期，通过 N-乙酰氨基葡萄糖部分 (O-GlcNAc) 的 O 键修饰的核和细胞质蛋白上的丝氨酸和苏氨酸残基的鉴定推翻了糖基化仅发生在内质网、高尔基体中的普遍假设。和分泌途径。与传统的糖基化相比，O-GlcNAc 修饰不会导致复杂的支链聚糖结构，并且分别通过 O-GlcNAc 转移酶 (OGT) 和 O-GlcNAc (OGA) 快速循环打开和关闭蛋白质。自发现以来，O-GlcNAcylation 已被证明有助于多种细胞功能，包括信号传导、蛋白质定位和稳定性、转录、染色质重塑、线粒体功能和细胞存活。O-GlcNAc 循环中的失调与糖尿病、糖尿病并发症、癌症、心血管和神经退行性疾病等多种疾病的进展有关。这篇综述将概述我们目前对调节 O-GlcNAc 转换过程的理解、O-GlcNAc 化在调节细胞生理学中的作用，以及 O-GlcNAc 循环中的失调如何促成病理生理过程。