Up-regulation of O-GlcNAc Transferase with Glucose Deprivation in HepG2 Cells Is Mediated by Decreased Hexosamine Pathway Flux
| Autor: | Jefferson H. Chambers, Taylor S. Geisler, Donald A. McClain, Rodrick P. Taylor |
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| Rok vydání: | 2009 |
| Předmět: |
Cytoplasm
medicine.medical_specialty Nutrient sensing AMP-Activated Protein Kinases Biology N-Acetylglucosaminyltransferases Biochemistry Acetylglucosamine chemistry.chemical_compound AMP-activated protein kinase Downregulation and upregulation Glucosamine Cell Line Tumor Internal medicine medicine Humans RNA Messenger Phosphorylation Enzyme inducer Glycogen synthase Molecular Biology Cell Nucleus Cell Biology Metabolism and Bioenergetics Glucose Glycogen Synthase Endocrinology chemistry Enzyme Induction biology.protein Protein Processing Post-Translational Flux (metabolism) |
| Zdroj: | Journal of Biological Chemistry. 284:3425-3432 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m803198200 |
| Popis: | O-Linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of proteins that functions as a nutrient sensing mechanism. We have previously shown a significant induction of O-GlcNAc modification under conditions of glucose deprivation. Increased O-GlcNAc modification was mediated by increased mRNA for nucleocytoplasmic O-linked N-acetylglucosaminyltransferase (ncOGT). We have investigated the mechanism mediating ncOGT induction with glucose deprivation. The signal does not appear to be general energy depletion because no differences in AMP-dependent kinase protein levels or phosphorylation were observed between glucose-deprived and normal glucose-treated cells. However, treatment of glucose-deprived cells with a small dose (1 mm) of glucosamine blocked the induction of ncOGT mRNA and subsequent increase in O-GlcNAc protein modification, suggesting that decreased hexosamine flux is the signal for ncOGT up-regulation. Consistent with this, treatment of glucose-deprived cells with an inhibitor of O-GlcNAcase (O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino N-phenyl carbamat) completely prevented the subsequent up-regulation of ncOGT. Glucosamine treatment also resulted in a 40% rescue of the down-regulation of glycogen synthase activity normally seen after glucose deprivation. We conclude that deglycosylation of proteins within the first few hours of glucose deprivation promotes ncOGT induction. These findings suggest a novel negative feedback regulatory loop for OGT and O-GlcNAc regulation. |
| Databáze: | OpenAIRE |
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