Regulatory Role of Glycogen Synthase Kinase 3 for Transcriptional Activity of ADD1/SREBP1c
| Autor: | Sung Sik Choe, Eung Jae Yoo, Min Jeong Song, Jae Bum Kim, Kang Ho Kim, Sang Dai Park |
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| Rok vydání: | 2004 |
| Předmět: |
Indoles
Transcription Genetic macromolecular substances In Vitro Techniques Biology Biochemistry Cell Line Maleimides Glycogen Synthase Kinase 3 Mice GSK-3 3T3-L1 Cells Gene expression Animals Humans Insulin Phosphorylation Glycogen synthase Molecular Biology GSK3B Glycogen Synthase Kinase 3 beta Base Sequence Lipid metabolism DNA Cell Biology Lipid Metabolism Recombinant Proteins Rats DNA-Binding Proteins Fatty acid synthase CCAAT-Enhancer-Binding Proteins biology.protein Signal transduction Lithium Chloride Sterol Regulatory Element Binding Protein 1 Signal Transduction Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 279:51999-52006 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m405522200 |
| Popis: | Adipocyte determination- and differentiation-dependent factor 1 (ADD1) plays important roles in lipid metabolism and insulin-dependent gene expression. Because insulin stimulates carbohydrate and lipid synthesis, it would be important to decipher how the transcriptional activity of ADD1/SREBP1c is regulated in the insulin signaling pathway. In this study, we demonstrated that glycogen synthase kinase (GSK)-3 negatively regulates the transcriptional activity of ADD1/SREBP1c. GSK3 inhibitors enhanced a transcriptional activity of ADD1/SREBP1c and expression of ADD1/SREBP1c target genes including fatty acid synthase (FAS), acetyl-CoA carboxylase 1 (ACC1), and steroyl-CoA desaturase 1 (SCD1) in adipocytes and hepatocytes. In contrast, overexpression of GSK3beta down-regulated the transcriptional activity of ADD1/SREBP1c. GSK3 inhibitor-mediated ADD1/SREBP1c target gene activation did not require de novo protein synthesis, implying that GSK3 might affect transcriptional activity of ADD1/SREBP1c at the level of post-translational modification. Additionally, we demonstrated that GSK3 efficiently phosphorylated ADD1/SREBP1c in vitro and in vivo. Therefore, these data suggest that GSK3 inactivation is crucial to confer stimulated transcriptional activity of ADD1/SREBP1c for insulin-dependent gene expression, which would coordinate lipid and glucose metabolism. |
| Databáze: | OpenAIRE |
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