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Trends Endocrinol Metab. 2013 Jun;24(6):301-9. doi: 10.1016/j.tem.2013.02.002. Epub 2013 May 4.

Cracking the O-GlcNAc code in metabolism.

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Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06519, USA.


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.

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