Abstract
UDP-N-acetylglucosamine/polypeptide-N-acetylglucosaminyltransferase or O-GlcNAc transferase catalyzes the transfer of an N-acetylglucosamine moiety from the donor substrate UDP-GlcNAc onto serine/threonine residues of nuclear and cytoplasmic proteins (Torres and Hart 1984). Discovered in the early 1980’s, this O-linked sugar modification better known as O-GlcNAcylation is different from other saccharide modification in that it does not get elongated to long oligosaccharide chains; is nuclear/cytosolic in nature; is sub-stoichiometric at individual sites, with rapid cycling dynamics; and functions as an important signaling moiety akin to protein phosphorylation. The cellular concentration of UDP-GlcNAc, the donor substrate for cellular O-GlcNAcylation, is highly responsive to glucose flux, amino acid and fatty acid metabolism, nucleotide biosynthesis, as well as flux through glycolysis and Kreb’s cycle (Marshall et al. 1991). Overall about 2–5 % of cellular glucose gets diverted towards the hexosamine biosynthetic pathway to produce UDP-GlcNAc. Since UDP-GlcNAc production is impacted by a number of metabolic pathways and the binding of UDP-GlcNAc to O-GlcNAc transferase varies over a wide range of substrate concentrations, O-GlcNAcylation functions as an excellent nutrient and stress sensor (Wells et al. 2001; Hart et al. 2007). O-GlcNAcylation also serves as an important regulatory PTM for a wide variety of biological pathways. Cell cycle progression, transcription, intracellular signaling, nutrient sensing, and neuronal plasticity are all affected by protein O-GlcNAcylation. Abnormalities in levels of O-GlcNAc have been shown to be an underlying cause of insulin resistance and glucose toxicity in diabetes, neurodegenerative disorders, and dysregulation of tumor suppressors and oncogenic proteins in cancer.
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Banerjee, P., Hart, G.W. (2014). O-Linked N-Acetylglucosamine (GlcNAc) Transferase (UDP-N-Acetylglucosamine: Polypeptide-N-Acetylglucosaminyl Transferase) (OGT). In: Taniguchi, N., Honke, K., Fukuda, M., Narimatsu, H., Yamaguchi, Y., Angata, T. (eds) Handbook of Glycosyltransferases and Related Genes. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54240-7_48
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DOI: https://doi.org/10.1007/978-4-431-54240-7_48
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