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Transcriptional activities of nuclear SREBP-1a, -1c,and -2 to different target promoters of lipogenic and cholesterogenic genes 总被引:5,自引:0,他引:5
Amemiya-Kudo M Shimano H Hasty AH Yahagi N Yoshikawa T Matsuzaka T Okazaki H Tamura Y Iizuka Y Ohashi K Osuga J Harada K Gotoda T Sato R Kimura S Ishibashi S Yamada N 《Journal of lipid research》2002,43(8):1220-1235
Recent studies on the in vivo roles of the sterol regulatory element binding protein (SREBP) family indicate that SREBP-2 is more specific to cholesterogenic gene expression whereas SREBP-1 targets lipogenic genes. To define the molecular mechanism involved in this differential regulation, luciferase-reporter gene assays were performed in HepG2 cells to compare the transactivities of nuclear SREBP-1a, -1c, and -2 on a battery of SREBP-target promoters containing sterol regulatory element (SRE), SRE-like, or E-box sequences. The results show first that cholesterogenic genes containing classic SREs in their promoters are strongly and efficiently activated by both SREBP-1a and SREBP-2, but not by SREBP-1c. Second, an E-box containing reporter gene is much less efficiently activated by SREBP-1a and -1c, and SREBP-2 was inactive in spite of its ability to bind to the E-box. Third, promoters of lipogenic enzymes containing variations of SRE (SRE-like sequences) are strongly activated by SREBP-1a, and only modestly and equally by both SREBP-1c and -2. Finally, substitution of the unique tyrosine residue within the basic helix-loop-helix (bHLH) portion of nuclear SREBPs with arginine, the conserved residue found in all other bHLH proteins, abolishes the transactivity of all SREBPs for SRE, and conversely results in markedly increased activity of SREBP-1 but not activity of SREBP-2 for E-boxes. These data demonstrate the different specificity and affinity of nuclear SREBP-1 and -2 for different target DNAs, explaining a part of the mechanism behind the differential in vivo regulation of cholesterogenic and lipogenic enzymes by SREBP-1 and -2, respectively. 相似文献
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SREBP transcription factors: master regulators of lipid homeostasis 总被引:41,自引:0,他引:41
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A crucial role of sterol regulatory element-binding protein-1 in the regulation of lipogenic gene expression by polyunsaturated fatty acids 总被引:19,自引:0,他引:19
Yahagi N Shimano H Hasty AH Amemiya-Kudo M Okazaki H Tamura Y Iizuka Y Shionoiri F Ohashi K Osuga J Harada K Gotoda T Nagai R Ishibashi S Yamada N 《The Journal of biological chemistry》1999,274(50):35840-35844
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Lipid synthetic transcription factor SREBP-1a activates p21WAF1/CIP1, a universal cyclin-dependent kinase inhibitor
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Inoue N Shimano H Nakakuki M Matsuzaka T Nakagawa Y Yamamoto T Sato R Takahashi A Sone H Yahagi N Suzuki H Toyoshima H Yamada N 《Molecular and cellular biology》2005,25(20):8938-8947
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Sterol regulatory element-binding proteins induce an entire pathway of cholesterol synthesis 总被引:2,自引:0,他引:2
Sakakura Y Shimano H Sone H Takahashi A Inoue N Toyoshima H Suzuki S Yamada N Inoue K 《Biochemical and biophysical research communications》2001,286(1):176-183
To evaluate the effects of sterol regulatory element-binding proteins (SREBPs) on the expression of the individual enzymes in the cholesterol synthetic pathway, we examined expression of these genes in the livers from wild-type and transgenic mice overexpressing nuclear SREBP-1a or -2. As estimated by a Northern blot analysis, overexpression of nuclear SREBP-1a or -2 caused marked increases in mRNA levels of the whole battery of cholesterogenic genes. This SREBP activation covers not only rate-limiting enzymes such as HMG CoA synthase and reductase that have been well established as SREBP targets, but also all the enzyme genes in the cholesterol synthetic pathway tested here. The activated genes include mevalonate kinase, mevalonate pyrophosphate decarboxylase, isopentenyl phosphate isomerase, geranylgeranyl pyrophosphate synthase, farnesyl pyrophosphate synthase, squalene synthase, squalene epoxidase, lanosterol synthase, lanosterol demethylase, and 7-dehydro-cholesterol reductase. These results demonstrate that SREBPs activate every step of cholesterol synthetic pathway, contributing to an efficient cholesterol synthesis. 相似文献
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Regulation of gene expression by SREBP and SCAP 总被引:22,自引:0,他引:22
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Spatial distribution and function of sterol regulatory element-binding protein 1a and 2 homo- and heterodimers by in vivo two-photon imaging and spectroscopy fluorescence resonance energy transfer
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Zoumi A Datta S Liaw LH Wu CJ Manthripragada G Osborne TF Lamorte VJ 《Molecular and cellular biology》2005,25(8):2946-2956
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Toth JI Datta S Athanikar JN Freedman LP Osborne TF 《Molecular and cellular biology》2004,24(18):8288-8300
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Regulation of Peroxisome Proliferator-Activated Receptor γ Expression by Adipocyte Differentiation and Determination Factor 1/Sterol Regulatory Element Binding Protein 1: Implications for Adipocyte Differentiation and Metabolism 总被引:1,自引:0,他引:1
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Lluis Fajas Kristina Schoonjans Laurent Gelman Jae B. Kim Jamila Najib Genevieve Martin Jean-Charles Fruchart Michael Briggs Bruce M. Spiegelman Johan Auwerx 《Molecular and cellular biology》1999,19(8):5495-5503
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