O-glycosylation of Sp1 and transcriptional regulation of the calmodulin gene by insulin and glucagon
| Autor: | Antonio Martinez-Hernandez, Rajendra Raghow, Gipsy Majumdar, Rosalind Pitpitan Candelaria, Solomon S. Solomon, Ashley D. Harmon |
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| Rok vydání: | 2003 |
| Předmět: |
Transcriptional Activation
medicine.medical_specialty Carcinoma Hepatocellular Glycosylation animal structures Sp1 Transcription Factor Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Gene Expression Biology Glucagon Streptozocin Acetylglucosamine Calmodulin Gastrointestinal Agents Transcription (biology) Physiology (medical) Internal medicine Norleucine Gene expression Tumor Cells Cultured medicine Transcriptional regulation Animals Hypoglycemic Agents Insulin RNA Messenger Pancreatic hormone Sp1 transcription factor Antibiotics Antineoplastic Subcellular localization Immunohistochemistry Rats carbohydrates (lipids) Endocrinology |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 285:E584-E591 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | Both insulin and glucagon stimulate steady-state levels of Sp1 transcription factor, but only insulin stimulates transcription of the calmodulin (CaM) gene in liver. Because O-glycosylation of Sp1 by O-linked N-acetylglucosamine ( O-GlcNAc) is thought to regulate its ability to activate transcription, we assayed the levels of Sp1 with anti-Sp1 and anti- O-GlcNAc antibodies in Western blots by use of extracts of H-411E liver cells treated with insulin (10,000 μU/ml) or glucagon (1.5 × 10-5M). We also assessed subcellular localization of the native and glycosylated Sp1 in H411E cells treated with either hormone in the presence of deoxynorleucine (DON, an indirect inhibitor of O-glycosylation) or streptozotocin (STZ, an indirect stimulator of O-glycosylation). Insulin stimulated both total and O-GlcNAc-modified Sp1 primarily in the nucleus and induced CaM gene transcription ( P < 0.0001). In contrast, glucagon promoted accumulation of Sp1 in the cytoplasm but not the nucleus, without significantly stimulating ( P = not significant) either its O-glycosylation or transcription of the CaM gene. DON inhibited O-glycosylation of Sp1 and its ability to migrate to the nucleus and transactivate CaM gene transcription. In contrast, cotreatment of cells with STZ and glucagon enhanced O-glycosylation of Sp1, promoting its migration to the nucleus and resulting in increased CaM gene transcription. Thus O-glycosylation of Sp1 by insulin, but not glucagon, apparently enhances its (Sp1) nuclear recruitment and results in activation of CaM gene transcription. |
| Databáze: | OpenAIRE |
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