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.
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Health (R01 DK089098, P01 DK057751), American Diabetes Association, and Ellison Medical Foundation to X.Y., the Brown-Coxe fellowship to H.R., the China Scholarship Council-Yale World Scholars fellowship to M.L., and the Xi’an Jiaotong University international cooperation grant to J.W.
- Cancer metabolism
- Circadian rhythm
- Hexosamine biosynthesis
- Insulin resistance