Genomes and Genes
Gene Symbol: SREBP-1
Description: sterol regulatory element binding transcription factor 1
Alias: SREBP1, bHLHd1, sterol regulatory element-binding protein 1, class D basic helix-loop-helix protein 1
- Sakai J, Nohturfft A, Cheng D, Ho Y, Brown M, Goldstein J. Identification of complexes between the COOH-terminal domains of sterol regulatory element-binding proteins (SREBPs) and SREBP cleavage-activating protein. J Biol Chem. 1997;272:20213-21 pubmed
- Walker A, Yang F, Jiang K, Ji J, Watts J, Purushotham A, et al. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev. 2010;24:1403-17 pubmed publisher..These findings may have important biomedical implications for the treatment of metabolic disorders associated with aberrant lipid/cholesterol homeostasis, including metabolic syndrome and atherosclerosis. ..
- Lin J, Yang R, Tarr P, Wu P, Handschin C, Li S, et al. Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. Cell. 2005;120:261-73 pubmed..These data suggest a mechanism through which dietary saturated fats can stimulate hyperlipidemia and atherogenesis. ..
- Kotzka J, Muller Wieland D. Sterol regulatory element-binding protein (SREBP)-1: gene regulatory target for insulin resistance?. Expert Opin Ther Targets. 2004;8:141-9 pubmed..The authors have recently shown that SREBPs are substrates of mitogen-activated protein kinases, and propose that SREBP-1 might play a role in the development of cellular features belonging to lipotoxicity and, possibly, syndrome X. ..
- Engelking L, Kuriyama H, Hammer R, Horton J, Brown M, Goldstein J, et al. Overexpression of Insig-1 in the livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis. J Clin Invest. 2004;113:1168-75 pubmed..These results provide in vivo support for the hypothesis that nSREBPs are essential for high levels of lipid synthesis in the liver and indicate that Insig's modulate nSREBP levels by binding and retaining SCAP in the ER. ..
- Lehr S, Kotzka J, Avci H, Knebel B, Muller S, Hanisch F, et al. Effect of sterol regulatory element binding protein-1a on the mitochondrial protein pattern in human liver cells detected by 2D-DIGE. Biochemistry. 2005;44:5117-28 pubmed..Therefore, the detected protein differences might be an explanation for the observed intracellular lipid accumulation and might link SREBP-1a to features like steatosis hepatis. ..
- Shimomura I, Shimano H, Horton J, Goldstein J, Brown M. Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J Clin Invest. 1997;99:838-45 pubmed..2-fold), and the 1c transcript remained virtually undetectable. We conclude that the SREBP-1a and 1c transcripts are controlled independently by regulatory regions that respond differentially to organ-specific and metabolic factors...
- Yabe D, Brown M, Goldstein J. Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proc Natl Acad Sci U S A. 2002;99:12753-8 pubmed publisher..The combined actions of insig-1 and -2 permit feedback regulation of cholesterol synthesis over a wide range of sterol concentrations...
- Liu J, Liu J, Guo Q, Liu J. [Association of sterol regulatory element binding protein-1c genetic polymorphisms rs2297508 and rs11868035 with type 2 diabetes mellitus in Gansu Han and Dongxiang population]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012;29:328-33 pubmed publisher..SNP rs2297508 of SREBP-1c gene may be associated with increased plasma levels of LDL-C in both Han or Dongxiang ethnics. ..
- Sewter C, Berger D, Considine R, Medina G, Rochford J, Ciaraldi T, et al. Human obesity and type 2 diabetes are associated with alterations in SREBP1 isoform expression that are reproduced ex vivo by tumor necrosis factor-alpha. Diabetes. 2002;51:1035-41 pubmed..Exposure of isolated human adipocytes to insulin enhanced SREBP1 gene expression and promoted its proteolytic cleavage to the active form...
- Ducluzeau P, Perretti N, Laville M, Andreelli F, Vega N, Riou J, et al. Regulation by insulin of gene expression in human skeletal muscle and adipose tissue. Evidence for specific defects in type 2 diabetes. Diabetes. 2001;50:1134-42 pubmed..This study thus provides evidence for a specific defect in the regulation of a group of important genes in response to insulin in peripheral tissues of type 2 diabetic patients. ..
- Kohjima M, Higuchi N, Kato M, Kotoh K, Yoshimoto T, Fujino T, et al. SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int J Mol Med. 2008;21:507-11 pubmed..These data indicate that, in NAFLD, insulin signaling via IRS-1 causes the up-regulation of SREBP1-c, leading to the increased synthesis of fatty acids by the hepatocytes; negative feedback regulation via AMPK ..
- Sundqvist A, Bengoechea Alonso M, Ye X, Lukiyanchuk V, Jin J, Harper J, et al. Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7). Cell Metab. 2005;1:379-91 pubmed..also degrades nuclear SREBP1c and SREBP2, and inactivation of endogenous Fbw7 results in stabilization of nuclear SREBP1 and -2, enhanced expression of SREBP target genes, enhanced synthesis of cholesterol and fatty acids, and enhanced ..
- Ferre P, Foufelle F. SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Horm Res. 2007;68:72-82 pubmed
- Hua X, Sakai J, Brown M, Goldstein J. Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane. J Biol Chem. 1996;271:10379-84 pubmed..These results indicate that sterol-regulated proteolysis of SREBPs is a complex process, requiring sequences on both sides of the ER membrane. ..
- Laudes M, Barroso I, Luan J, Soos M, Yeo G, Meirhaeghe A, et al. Genetic variants in human sterol regulatory element binding protein-1c in syndromes of severe insulin resistance and type 2 diabetes. Diabetes. 2004;53:842-6 pubmed
- Vedie B, Jeunemaitre X, Megnien J, Atger V, Simon A, Moatti N. A new DNA polymorphism in the 5' untranslated region of the human SREBP-1a is related to development of atherosclerosis in high cardiovascular risk population. Atherosclerosis. 2001;154:589-97 pubmed..311, P=0.03). Thus, we have identified a new polymorphism in the 5' untranslated region of the SREBP-1a gene, and demonstrated its association with an atherogenic lipid profile and echographic plaques. ..
- Yang Y, Morin P, Han W, Chen T, Bornman D, Gabrielson E, et al. Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c. Exp Cell Res. 2003;282:132-7 pubmed..We conclude that regulation of FAS expression in breast cancer is achieved through modulation of SREBP-1c, similar to the regulation in liver and adipose tissue, although the upstream regulation of liopgenesis differs in these tissues. ..
- Roth G, Kotzka J, Kremer L, Lehr S, Lohaus C, Meyer H, et al. MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein (SREBP)-1a at serine 117 in vitro. J Biol Chem. 2000;275:33302-7 pubmed..Our data indicate that the MAP kinase-mediated effects on SREBP-1a-regulated target genes are linked to this phosphorylation site. ..
- Dubuquoy C, Robichon C, Lasnier F, Langlois C, Dugail I, Foufelle F, et al. Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in mouse and human hepatocytes. J Hepatol. 2011;55:145-53 pubmed publisher..All together, our results suggest that adiponutrin/PNPLA3 is regulated by two key factors of the glycolytic and lipogenic pathways, raising the question of its implication in the metabolism of carbohydrates and lipids. ..
- Najafi Shoushtari S, Kristo F, Li Y, Shioda T, Cohen D, Gerszten R, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010;328:1566-9 pubmed publisher..Our findings indicate that miR-33 acts in concert with the SREBP host genes to control cholesterol homeostasis and suggest that miR-33 may represent a therapeutic target for ameliorating cardiometabolic diseases...
- Lecomte V, Meugnier E, Euthine V, Durand C, Freyssenet D, Nemoz G, et al. A new role for sterol regulatory element binding protein 1 transcription factors in the regulation of muscle mass and muscle cell differentiation. Mol Cell Biol. 2010;30:1182-98 pubmed publisher..In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis...
- Taghibiglou C, Martin H, Lai T, Cho T, Prasad S, Kojic L, et al. Role of NMDA receptor-dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries. Nat Med. 2009;15:1399-406 pubmed publisher..Our study suggests that agents that reduce SREBP-1 activation such as Indip may represent a new class of neuroprotective therapeutics against stroke. ..
- Arito M, Horiba T, Hachimura S, Inoue J, Sato R. Growth factor-induced phosphorylation of sterol regulatory element-binding proteins inhibits sumoylation, thereby stimulating the expression of their target genes, low density lipoprotein uptake, and lipid synthesis. J Biol Chem. 2008;283:15224-31 pubmed publisher..In summary, growth factors inhibit sumoylation of SREBPs through their phosphorylation, thus avoiding the recruitment of an HDAC3 corepressor complex and stimulating the lipid uptake and synthesis required for cell growth. ..
- Le Hellard S, Theisen F, Haberhausen M, Raeder M, Fernø J, Gebhardt S, et al. Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects?. Mol Psychiatry. 2009;14:308-17 pubmed publisher..Our finding is supported by the recent involvement of the INSIG2 gene in obesity in the general population and implicates SREBP-controlled lipogenesis in drug-induced metabolic adverse effects. ..
- Gosmain Y, Lefai E, Ryser S, Roques M, Vidal H. Sterol regulatory element-binding protein-1 mediates the effect of insulin on hexokinase II gene expression in human muscle cells. Diabetes. 2004;53:321-9 pubmed..These results demonstrate that SREBP-1c is involved in the effect of insulin on HKII gene transcription and indicate that it is one of the mediators of insulin action on gene expression in human skeletal muscle. ..
- Felder T, Oberkofler H, Weitgasser R, Mackevics V, Krempler F, Paulweber B, et al. The SREBF-1 locus is associated with type 2 diabetes and plasma adiponectin levels in a middle-aged Austrian population. Int J Obes (Lond). 2007;31:1099-103 pubmed..Our results therefore raise the possibility that sequence variations at the SREBF-1 gene locus might contribute to T2DM risk, at least in part, by altering circulating adiponectin levels. ..
- Nie L, Lu Q, Li W, Yang N, Dongol S, Zhang X, et al. Sterol regulatory element-binding protein 1 is required for ovarian tumor growth. Oncol Rep. 2013;30:1346-54 pubmed publisher..of lipogenic enzymes, most of which are transcriptional targets of sterol regulatory element-binding protein 1 (SREBP1). However, the expression levels and the function of SREBP1 in ovarian cancer are largely unknown...
- Salek L, Lutucuta S, Ballantyne C, Gotto A, Marian A. Effects of SREBF-1a and SCAP polymorphisms on plasma levels of lipids, severity, progression and regression of coronary atherosclerosis and response to therapy with fluvastatin. J Mol Med (Berl). 2002;80:737-44 pubmed..There were no significant interactions between SCAP genotypes and response to therapy. Thus we detected a strong graded interaction between SREBF-1a -36del/G genotypes and response of plasma apoA-I to treatment with fluvastatin. ..
- Yamashita T, Honda M, Takatori H, Nishino R, Minato H, Takamura H, et al. Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma. J Hepatol. 2009;50:100-10 pubmed publisher..The lipogenic pathway is activated in a subset of HCC and contributes to cell proliferation and prognosis. ..
- Kotzka J, Muller Wieland D, Roth G, Kremer L, Munck M, Schurmann S, et al. Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade. J Lipid Res. 2000;41:99-108 pubmed..We conclude that SREBP-1a and SREBP-2 mediate different regulatory effects converging at sre-1 and that they appear to be linked to the MAP kinase cascade, possibly being direct substrates of ERK1 and ERK2. ..
- Liu J, Liu J, Li P, Xie X, Guo Q, Tian L, et al. Association of sterol regulatory element-binding protein-1c gene polymorphism with type 2 diabetes mellitus, insulin resistance and blood lipid levels in Chinese population. Diabetes Res Clin Pract. 2008;82:42-7 pubmed publisher..Moreover, the SNP (rs11868035) is closely related to insulin resistance (IR) in diabetic patients. ..
- Harding A, Loos R, Luan J, O Rahilly S, Wareham N, Barroso I. Polymorphisms in the gene encoding sterol regulatory element-binding factor-1c are associated with type 2 diabetes. Diabetologia. 2006;49:2642-8 pubmed..In summary, we replicated our previous finding and found evidence for SNPs in the 5' region of the SREBF1c gene to be associated with the risk of type 2 diabetes and plasma glucose concentration. ..
- Fiegenbaum M, Silveira F, Van der Sand C, Van der Sand L, Ferreira M, Pires R, et al. Determinants of variable response to simvastatin treatment: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes. Pharmacogenomics J. 2005;5:359-64 pubmed..8%), whereas only 29% of 2386A homozygous reached this reduction (P=0.009). Our data suggest that the SCAP 2386A>G gene polymorphism was a significant predictor of TC and triglyceride responses to simvastatin treatment. ..
- Ponugoti B, Kim D, Xiao Z, Smith Z, Miao J, Zang M, et al. SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. J Biol Chem. 2010;285:33959-70 pubmed publisher..Reducing acetylation of SREBP-1c by targeting SIRT1 may be useful for treating metabolic disorders, including fatty liver, obesity, and type II diabetes...
- Shimomura I, Matsuda M, Hammer R, Bashmakov Y, Brown M, Goldstein J. Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Mol Cell. 2000;6:77-86 pubmed..The combination of insulin resistance (inappropriate gluconeogenesis) and insulin sensitivity (elevated lipogenesis) establishes a vicious cycle that aggravates hyperinsulinemia and insulin resistance in lipodystrophic and ob/ob mice. ..
- Nagata R, Nishio Y, Sekine O, Nagai Y, Maeno Y, Ugi S, et al. Single nucleotide polymorphism (-468 Gly to A) at the promoter region of SREBP-1c associates with genetic defect of fructose-induced hepatic lipogenesis [corrected]. J Biol Chem. 2004;279:29031-42 pubmed..loss of binding of unidentified proteins to the region between -453 to -480 bp of the SREBP-1c promoter and 2). impaired insulin stimulation of SREBP-1c promoter activity. ..
- Li W, Tai Y, Zhou J, Gu W, Bai Z, Zhou T, et al. Repression of endometrial tumor growth by targeting SREBP1 and lipogenesis. Cell Cycle. 2012;11:2348-58 pubmed publisher..The sterol regulatory element-binding protein 1 (SREBP1), encoded by SREBF1 gene, is a master regulator of lipogenic gene expression...
- Takahashi A, Motomura K, Kato T, Yoshikawa T, Nakagawa Y, Yahagi N, et al. Transgenic mice overexpressing nuclear SREBP-1c in pancreatic beta-cells. Diabetes. 2005;54:492-9 pubmed..Taken together with enhanced insulin secretion from SREBP-1-null islets, these data suggest that SREBP-1c and endogenous lipogenesis could be involved in beta-cell dysfunction and diabetes. ..
- Kotzka J, Knebel B, Janssen O, Schaefer J, Soufi M, Jacob S, et al. Identification of a gene variant in the master regulator of lipid metabolism SREBP-1 in a family with a novel form of severe combined hypolipidemia. Atherosclerosis. 2011;218:134-43 pubmed publisher..Phosphorylation of SREBP-1, the master regulator of genes for central rate limiting enzymes of cholesterol and lipid metabolism, appears to be a biological principle with clinical implications. ..
- Amemiya Kudo M, Shimano H, Hasty A, Yahagi N, Yoshikawa T, Matsuzaka T, et al. Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target promoters of lipogenic and cholesterogenic genes. J Lipid Res. 2002;43:1220-35 pubmed
- Campa D, McKay J, Sinilnikova O, Husing A, Vogel U, Hansen R, et al. Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk. Breast Cancer Res Treat. 2009;118:565-74 pubmed publisher..On the other hand, we found that two SNPs in FASN were associated with BMI. ..
- McPherson S, Jonsson J, Barrie H, O Rourke P, Clouston A, Powell E. Investigation of the role of SREBP-1c in the pathogenesis of HCV-related steatosis. J Hepatol. 2008;49:1046-54 pubmed publisher..HCV-infected patients with HOMA>2 had significantly higher expression of FAS mRNA than HCV-infected subjects with HOMA2 (p=0.006) and NDL (p=0.016). SREBP-1c may not play a prominent role in the pathogenesis of HCV-related steatosis. ..
- Grarup N, Stender Petersen K, Andersson E, Jørgensen T, Borch Johnsen K, Sandbaek A, et al. Association of variants in the sterol regulatory element-binding factor 1 (SREBF1) gene with type 2 diabetes, glycemia, and insulin resistance: a study of 15,734 Danish subjects. Diabetes. 2008;57:1136-42 pubmed publisher..Because sterol regulatory element-binding protein-1c is a mediator of insulin action, the findings are consistent with the presence of a yet undefined subtle loss-of-function SREBF1 variant. ..
- Chakravarty K, Wu S, Chiang C, Samols D, Hanson R. SREBP-1c and Sp1 interact to regulate transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in the liver. J Biol Chem. 2004;279:15385-95 pubmed..We propose that insulin represses transcription of the gene for PEPCK-C by inducing SREBP-1c production in the liver, which interferes with the stimulatory effect of Sp1 at -590 of the PEPCK-C gene promoter. ..
- Eberle D, Clement K, Meyre D, Sahbatou M, Vaxillaire M, Le Gall A, et al. SREBF-1 gene polymorphisms are associated with obesity and type 2 diabetes in French obese and diabetic cohorts. Diabetes. 2004;53:2153-7 pubmed..03) and increased prevalence of nephropathy (P = 0.028) in a diabetic cohort. Our results indicate a role of the SREBF-1 gene in genetic predisposition of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. ..
- Szydlowski M, Kiliszek P, Sewastianik T, Jablonska E, Bialopiotrowicz E, Gorniak P, et al. FOXO1 activation is an effector of SYK and AKT inhibition in tonic BCR signal-dependent diffuse large B-cell lymphomas. Blood. 2016;127:739-48 pubmed publisher..cells is also involved in regulation of expression of the critical master regulator of cholesterol biosynthesis, SREBP1. Because HRK is the key effector of SYK inhibition, we characterized a mechanism linking FOXO1 activation and HRK ..
- Gaspar J, Mathieu J, Alvarez P. 2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway. Sci Rep. 2017;7:2197 pubmed publisher..show that HPβCD addition mitigates these adverse effects in human fibroblasts by significantly reducing LDLr and SREBP1 gene expression...
- Dessalle K, Euthine V, Chanon S, Delarichaudy J, Fujii I, Rome S, et al. SREBP-1 transcription factors regulate skeletal muscle cell size by controlling protein synthesis through myogenic regulatory factors. PLoS ONE. 2012;7:e50878 pubmed publisher..Our results point out the roles of MRFs in the maintenance of the protein content and cell size in adult muscle fibre, and contribute to decipher the mechanisms by which SREBP-1 regulate muscle mass. ..
- Takeuchi Y, Yahagi N, Aita Y, Murayama Y, Sawada Y, Piao X, et al. KLF15 Enables Rapid Switching between Lipogenesis and Gluconeogenesis during Fasting. Cell Rep. 2016;16:2373-86 pubmed publisher..These findings reveal a key molecular link between glucose and lipid metabolism and have therapeutic implications for the treatment of hyperlipidemia. ..