Maturation and activity of sterol regulatory element binding protein 1 is inhibited by acyl-CoA binding domain containing 3
| العنوان: | Maturation and activity of sterol regulatory element binding protein 1 is inhibited by acyl-CoA binding domain containing 3 |
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| المؤلفون: | Sookhee Bang, Natalie R. Cohen, Sangwon F. Kim, Vishala Patel, Yong Chen, John S. Millar |
| المصدر: | PLoS ONE, Vol 7, Iss 11, p e49906 (2012) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Protein Conformation, lcsh:Medicine, Biochemistry, 0302 clinical medicine, Molecular Cell Biology, Homeostasis, Luciferases, lcsh:Science, 0303 health sciences, Gene knockdown, Multidisciplinary, biology, Fatty Acids, Lipids, Cellular Structures, Fatty acid synthase, 030220 oncology & carcinogenesis, Gene Knockdown Techniques, Lipogenesis, Medicine, Metabolic Pathways, Sterol Regulatory Element Binding Protein 1, Binding domain, Research Article, Cell Fractionation, 03 medical and health sciences, DNA-binding proteins, Humans, Immunoprecipitation, Obesity, Transcription factor, Biology, 030304 developmental biology, Nutrition, Adaptor Proteins, Signal Transducing, lcsh:R, Proteins, Protein interactions, Membrane Proteins, Lipid metabolism, Lipid Metabolism, Sterol regulatory element-binding protein, Metabolism, Subcellular Organelles, Gene Expression Regulation, biology.protein, lcsh:Q, Fatty Acid Synthases |
| الوصف: | Imbalance of lipid metabolism has been linked with pathogenesis of a variety of human pathological conditions such as diabetes, obesity, cancer and neurodegeneration. Sterol regulatory element binding proteins (SREBPs) are the master transcription factors controlling the homeostasis of fatty acids and cholesterol in the body. Transcription, expression, and activity of SREBPs are regulated by various nutritional, hormonal or stressful stimuli, yet the molecular and cellular mechanisms involved in these adaptative responses remains elusive. In the present study, we found that overexpressed acyl-CoA binding domain containing 3 (ACBD3), a Golgi-associated protein, dramatically inhibited SREBP1-sensitive promoter activity of fatty acid synthase (FASN). Moreover, lipid deprivation-stimulated SREBP1 maturation was significantly attenuated by ACBD3. With cell fractionation, gene knockdown and immunoprecipitation assays, it was showed that ACBD3 blocked intracellular maturation of SREBP1 probably through directly binding with the lipid regulator rather than disrupted SREBP1-SCAP-Insig1 interaction. Further investigation revealed that acyl-CoA domain-containing N-terminal sequence of ACBD3 contributed to its inhibitory effects on the production of nuclear SREBP1. In addition, mRNA and protein levels of FASN and de novo palmitate biosynthesis were remarkably reduced in cells overexpressed with ACBD3. These findings suggest that ACBD3 plays an essential role in maintaining lipid homeostasis via regulating SREBP1's processing pathway and thus impacting cellular lipogenesis. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4993e9ad043d8b5f8b5a8b95add17a0Test http://europepmc.org/articles/PMC3498211?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a4993e9ad043d8b5f8b5a8b95add17a0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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