Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06519, USA.
Trends Endocrinol Metab. 2013 Jun;24(6):301-9. doi: 10.1016/j.tem.2013.02.002. Epub 2013 May 4.
Nuclear, cytoplasmic, and mitochondrial proteins are extensively modified by O-linked β-N-acetylglucosamine (O-GlcNAc) moieties. This sugar modification regulates fundamental cellular processes in response to diverse nutritional and hormonal cues. The enzymes O-GlcNAc transferase (OGT) and O-linked β-N-acetylglucosaminase (O-GlcNAcase) mediate the addition and removal of O-GlcNAc, respectively. Aberrant O-GlcNAcylation has been implicated in a plethora of human diseases, including diabetes, cancer, aging, cardiovascular disease, and neurodegenerative disease. Because metabolic dysregulation is a vital component of these diseases, unraveling the roles of O-GlcNAc in metabolism is of emerging importance. Here, we review the current understanding of the functions of O-GlcNAc in cell signaling and gene transcription involved in metabolism, and focus on its relevance to diabetes, cancer, circadian rhythm, and mitochondrial function.
核、细胞质和线粒体蛋白广泛受到 O-连接β-N-乙酰葡萄糖胺 (O-GlcNAc) 修饰。这种糖修饰可响应各种营养和激素信号调节基本的细胞过程。O-连接β-N-乙酰葡萄糖胺转移酶 (OGT) 和 O-连接β-N-乙酰氨基葡萄糖苷酶 (O-GlcNAcase) 分别介导 O-GlcNAc 的添加和去除。异常的 O-GlcNAc 化与多种人类疾病有关，包括糖尿病、癌症、衰老、心血管疾病和神经退行性疾病。由于代谢失调是这些疾病的重要组成部分，因此揭示 O-GlcNAc 在代谢中的作用具有重要意义。在这里，我们综述了目前对 O-GlcNAc 在涉及代谢的细胞信号转导和基因转录中的功能的理解，并重点介绍了其与糖尿病、癌症、昼夜节律和线粒体功能的相关性。
