O-Linked N-Acetylglucosamine (GlcNAc) Transferase (UDP-N-Acetylglucosamine: Polypeptide-N-Acetylglucosaminyl Transferase) (OGT)
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.
KeywordsSubstrate Peptide Glycosyl Transferase Trimeric Complex Hydroxyl Amino Hexosamine Biosynthetic Pathway
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