title: Functional O-GlcNAc modifications: implications in molecular regulation and pathophysiology.
abstract: O-linked β-N-acetylglucosamine (O-GlcNAc) is a regulatory post-translational modification of intracellular proteins. The dynamic and inducible cycling of the modification is governed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in response to UDP-GlcNAc levels in the hexosamine biosynthetic pathway (HBP). Due to its reliance on glucose flux and substrate availability, a major focus in the field has been on how O-GlcNAc contributes to metabolic disease. For years this post-translational modification has been known to modify thousands of proteins implicated in various disorders, but direct functional connections have until recently remained elusive. New research is beginning to reveal the specific mechanisms through which O-GlcNAc influences cell dynamics and disease pathology including clear examples of O-GlcNAc modification at a specific site on a given protein altering its biological functions. The following review intends to focus primarily on studies in the last half decade linking O-GlcNAc modification of proteins with chromatin-directed gene regulation, developmental processes, and several metabolically related disorders including Alzheimer's, heart disease and cancer. These studies illustrate the emerging importance of this post-translational modification in biological processes and multiple pathophysiologies.
authors: Complex Carbohydrate Research Center, University of Georgia, Athens, USA.
authors: Krithika
authors: K
authors: Vaidyanathan
authors: Complex Carbohydrate Research Center, University of Georgia, Athens, USA.
authors: Sean
authors: S
authors: Durning
authors: Complex Carbohydrate Research Center, University of Georgia, Athens, USA.
authors: Lance
authors: L
authors: Wells
mesh_terms: D000117:Acetylglucosamine / Q000235:genetics / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008659:Metabolic Diseases / Q000235:genetics / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D011506:Proteins; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine