SREBF2

Summary

Gene Symbol: SREBF2
Description: sterol regulatory element binding transcription factor 2
Alias: SREBP-2, SREBP2, bHLHd2, sterol regulatory element-binding protein 2, class D basic helix-loop-helix protein 2
Species: human
Products:     SREBF2

Top Publications

  1. Yokoyama C, Wang X, Briggs M, Admon A, Wu J, Hua X, et al. SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell. 1993;75:187-97 pubmed
    ..We suggest that SREBP-1 is regulated by an unknown factor that is overwhelmed when SREBP-1 is overexpressed. Understanding the regulation of SREBP-1 may be crucial for understanding the control of plasma cholesterol in humans. ..
  2. 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. ..
  3. Alrefai W, Annaba F, Sarwar Z, Dwivedi A, Saksena S, Singla A, et al. Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Am J Physiol Gastrointest Liver Physiol. 2007;292:G369-76 pubmed
    ..Our study demonstrated the modulation of human NPC1L1 expression and promoter activity by cholesterol in a SREBP-2-dependent mechanism. ..
  4. Hua X, Yokoyama C, Wu J, Briggs M, Brown M, Goldstein J, et al. SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc Natl Acad Sci U S A. 1993;90:11603-7 pubmed
    ..At high levels transcription reached a maximum, and the effects were no longer additive. The reason for the existence of two SREBPs and the mechanism by which they are regulated by sterols remain to be determined. ..
  5. Grimsby S, Jaensson H, Dubrovska A, Lomnytska M, Hellman U, Souchelnytskyi S. Proteomics-based identification of proteins interacting with Smad3: SREBP-2 forms a complex with Smad3 and inhibits its transcriptional activity. FEBS Lett. 2004;577:93-100 pubmed
    ..We found that SREBP-2 inhibited the transcriptional activity of Smad3 in luciferase reporter assays. ..
  6. Yaju D, Ruixing Y, Yiyang L, Yijiang Z, Weixiong L, Shangling P, et al. Polymorphism of the sterol regulatory element-binding protein-2 gene and its association with serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations. Am J Med Sci. 2009;337:14-22 pubmed
    ..The individuals carrying the G allele have more favorable lipid profiles than those carrying the C allele in Han but not in Hei Yi Zhuang. ..
  7. Hua X, Wu J, Goldstein J, Brown M, Hobbs H. Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13. Genomics. 1995;25:667-73 pubmed
    ..The genes for SREBP1 (SREBF1) and SREBP2 (SREBF2) have not been studied. In this paper we describe the cloning and characterization of the human SREBF1 gene...
  8. 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. ..
  9. Miserez A, Cao G, Probst L, Hobbs H. Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2). Genomics. 1997;40:31-40 pubmed
    ..In this paper we describe the gene structure and 5'-flanking sequence of SREBF2. SREBF2 spans 72 kb and is composed of 19 exons and 18 introns...

More Information

Publications110 found, 100 shown here

  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
  2. Yang T, Espenshade P, Wright M, Yabe D, Gong Y, Aebersold R, et al. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell. 2002;110:489-500 pubmed
    ..Mutant SCAP(Y298C) fails to bind INSIG-1 and is resistant to sterol-mediated inhibition of ER exit. By facilitating sterol-dependent ER retention of SCAP, INSIG-1 plays a central role in cholesterol homeostasis. ..
  3. Robinet P, Vedie B, Chironi G, Gariepy J, Simon A, Moatti N, et al. Characterization of polymorphic structure of SREBP-2 gene: role in atherosclerosis. Atherosclerosis. 2003;168:381-7 pubmed
    ..Thus, a common variation in the SREBP-2 gene is related with early-stage carotid atherosclerosis in subjects with a risk of cardiovascular events without detectable change in plasma lipid levels. ..
  4. Duan X, Zhu W, Li Y, Zhang Z, Zhao Y, Dao J, et al. The effect of sterol regulatory element-binding protein 2 polymorphism on the serum lipid in northern Chinese subjects. J Lipid Res. 2005;46:252-7 pubmed
    ..Further work is necessary to confirm the role of 1784G>C in the development of hyperlipidemia. ..
  5. Friedlander Y, Schwartz S, Durst R, Meiner V, Robertson A, Erez G, et al. SREBP-2 and SCAP isoforms and risk of early onset myocardial infarction. Atherosclerosis. 2008;196:896-904 pubmed
    ..S. men. The SCAP polymorphism appeared to modify the associations of SREBF-2 genotype with MI risk among men. These novel findings require confirmation in other populations. ..
  6. Liu X, Li Y, Lu X, Wang L, Zhao Q, Yang W, et al. Interactions among genetic variants from SREBP2 activating-related pathway on risk of coronary heart disease in Chinese Han population. Atherosclerosis. 2010;208:421-6 pubmed publisher
    ..We conducted a case-control study to investigate whether the common variants of genes from the SREBP2 activating-related pathway, involving SREBP2, SCAP, INSIG1 and INSIG2 genes, were associated with coronary heart ..
  7. 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...
  8. Yeh M, Cole A, Choi J, Liu Y, Tulchinsky D, Qiao J, et al. Role for sterol regulatory element-binding protein in activation of endothelial cells by phospholipid oxidation products. Circ Res. 2004;95:780-8 pubmed
    ..The current studies suggest a novel role for endothelial cholesterol depletion and subsequent SREBP activation in inflammatory processes in which phospholipid oxidation products accumulate. ..
  9. Durst R, Jansen A, Erez G, Bravdo R, Butbul E, Ben Avi L, et al. The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of plasma lipids among familial hypercholesterolaemia patients. Atherosclerosis. 2006;189:443-50 pubmed
    ..Further investigation is needed to confirm this effect. A study in a larger FH group or in non-FH hypercholesterolaemic subjects may further define the role of this regulatory mechanism in determining plasma lipid concentration. ..
  10. 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
    ..that the major genes involved in the SREBP activation of fatty acids and cholesterol production (SREBF1, SREBF2, SCAP, INSIG1 and INSIG2) would be strong candidate genes for interindividual variation in drug-induced weight ..
  11. Radhakrishnan A, Goldstein J, McDonald J, Brown M. Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance. Cell Metab. 2008;8:512-21 pubmed publisher
    ..Cooperative interactions between cholesterol, Scap, and Insig create a sensitive switch that controls the cholesterol composition of cell membranes with remarkable precision. ..
  12. Simon Y, Kessler S, Gemperlein K, Bohle R, Müller R, Haybaeck J, et al. Elevated free cholesterol in a p62 overexpression model of non-alcoholic steatohepatitis. World J Gastroenterol. 2014;20:17839-50 pubmed publisher
    ..due to increased cholesterol biosynthesis via elevated sterol regulatory element binding transcription factor 2 (SREBF2) gene expression and increased iron deposition in transgenic animals...
  13. Lim E, Lim J, Kim E, Kim Y, Shin J, Seok P, et al. Xylobiose, an Alternative Sweetener, Ameliorates Diabetes-Related Metabolic Changes by Regulating Hepatic Lipogenesis and miR-122a/33a in db/db Mice. Nutrients. 2016;8: pubmed
    ..These data demonstrate that XB exhibits anti-diabetic, hypolipogenic, and anti-inflammatory effects via regulation of the miR-122a/33a axis in db/db mice. ..
  14. Oishi K, Yamamoto S, Itoh N, Nakao R, Yasumoto Y, Tanaka K, et al. Wheat alkylresorcinols suppress high-fat, high-sucrose diet-induced obesity and glucose intolerance by increasing insulin sensitivity and cholesterol excretion in male mice. J Nutr. 2015;145:199-206 pubmed publisher
    ..4%, while upregulating the expression of hepatic cholesterol synthetic genes such as sterol regulatory element binding protein 2 (Srebf2) and 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1)...
  15. Hong M, Beidler J, Hooshmand S, Figueroa A, Kern M. Watermelon and l-arginine consumption improve serum lipid profile and reduce inflammation and oxidative stress by altering gene expression in rats fed an atherogenic diet. Nutr Res. 2018;58:46-54 pubmed publisher
    ..050). The results support the hypothesis that watermelon and arginine improve cardiovascular disease risk factors including lipid profile, antioxidant capacity, and inflammation by altering relevant gene expression. ..
  16. Sun J, Liu X, Cong L, Li H, Zhang C, Chen J, et al. Metabolomics study of the therapeutic mechanism of Schisandra Chinensis lignans in diet-induced hyperlipidemia mice. Lipids Health Dis. 2017;16:145 pubmed publisher
    ..Anti-hyperlipidemia effect of SCL was confirmed by both serum biochemistry and metabolomics analysis. The mechanism may be related to the down-regulation of LXRα/SREBP-1c/FAS/ACC and SREBP2/HMGCR signaling pathways.
  17. Hong M, Hartig N, Kaufman K, Hooshmand S, Figueroa A, Kern M. Watermelon consumption improves inflammation and antioxidant capacity in rats fed an atherogenic diet. Nutr Res. 2015;35:251-8 pubmed publisher
    ..05). These findings indicate that watermelon improves risk factors for CVD in rats through better lipid profiles, lower inflammation, and greater antioxidant capacity by altering gene expression for lipid metabolism. ..
  18. Atshaves B, McIntosh A, Martin G, Landrock D, Payne H, Bhuvanendran S, et al. Overexpression of sterol carrier protein-2 differentially alters hepatic cholesterol accumulation in cholesterol-fed mice. J Lipid Res. 2009;50:1429-47 pubmed publisher
    ..involved in cholesterol transport (L-FABP and SR-B1), cholesterol synthesis (related to sterol regulatory element binding protein 2 and HMG-CoA reductase), and bile acid oxidation/transport (via Oapt1a1, Oatp1a4, and SCP-x)...
  19. Schmitz G, Langmann T. Transcriptional regulatory networks in lipid metabolism control ABCA1 expression. Biochim Biophys Acta. 2005;1735:1-19 pubmed
    ..is mediated by corepressor complexes involving unliganded LXR, sterol-regulatory element binding protein 2 (SREBP2), Sp3, and the SCAN-domain protein ZNF202, which also impacts nuclear receptor signaling...
  20. Kuo Y, Lin C, Shih C. Ergostatrien-3β-ol from Antrodia camphorata inhibits diabetes and hyperlipidemia in high-fat-diet treated mice via regulation of hepatic related genes, glucose transporter 4, and AMP-activated protein kinase phosphorylation. J Agric Food Chem. 2015;63:2479-89 pubmed publisher
    ..Moreover, EK100-treated mice reduced blood TC levels by decreased hepatic expressions of SREBP2, which plays a major role in the regulation of cholesterol synthesis...
  21. Meljon A, Crick P, Yutuc E, Yau J, Seckl J, Theofilopoulos S, et al. Mining for Oxysterols in Cyp7b1-/- Mouse Brain and Plasma: Relevance to Spastic Paraplegia Type 5. Biomolecules. 2019;9: pubmed publisher
    ..The Cyp7b1-/- mouse does not show a motor defect; whether the defect in humans is a consequence of less efficient homeostasis of cholesterol in brain has yet to be uncovered. ..
  22. Wang X, Zhan X, Li X, Yu J, Liu X. MicroRNA-185 regulates expression of lipid metabolism genes and improves insulin sensitivity in mice with non-alcoholic fatty liver disease. World J Gastroenterol. 2014;20:17914-23 pubmed publisher
    ..These findings suggest that miR-185 plays an important role in regulating fatty-acid metabolism and cholesterol homeostasis in hepatocytes, as well as in improving insulin sensitivity, both in vitro and in vivo. ..
  23. Gil Ramírez A, Caz V, Martin Hernandez R, Marín F, Largo C, Rodríguez Casado A, et al. Modulation of cholesterol-related gene expression by ergosterol and ergosterol-enriched extracts obtained from Agaricus bisporus. Eur J Nutr. 2016;55:1041-57 pubmed publisher
    ..induced in jejunum a similar transcriptional response to simvastatin and ezetimibe; they all down-regulated Srebf2 and Nr1h4 (FXR) genes. Ergosterol-containing extracts from A...
  24. Jang Y, Park B, Lee H, Park H, Koo H, Kim B, et al. Sinigrin attenuates the progression of atherosclerosis in ApoE-/- mice fed a high-cholesterol diet potentially by inhibiting VCAM-1 expression. Chem Biol Interact. 2017;272:28-36 pubmed publisher
    ..Overall, sinigrin has the potential to be used in reducing the risks of atherosclerosis. ..
  25. Wang L, Zhu H, Zhao Y, Jiao R, Lei L, Chen J, et al. Cranberry anthocyanin as an herbal medicine lowers plasma cholesterol by increasing excretion of fecal sterols. Phytomedicine. 2018;38:98-106 pubmed publisher
    ..hepatic cholesterol-7?-hydroxylase (CYP7A1), 3-Hydroxy-3-methylglutaryl reductase (HMG-CoA-R), sterol regulatory element binding protein 2 (SREBP2), LDL receptor (LDL-R), and Liver X receptor alpha (LXR?)...
  26. Feng S, Han M, Zhou L, Wang Q, Li Z, Li Y, et al. NS5ABP37 inhibits liver cancer by impeding lipogenesis and cholesterogenesis. Cancer Sci. 2017;108:12-22 pubmed publisher
    ..Furthermore, NS5ABP37 overexpression decreased SREBP1c and SREBP2 levels by reducing their respective promoters...
  27. Zhao K, Chen Y, Penner G, Oba M, Guan L. Transcriptome analysis of ruminal epithelia revealed potential regulatory mechanisms involved in host adaptation to gradual high fermentable dietary transition in beef cattle. BMC Genomics. 2017;18:976 pubmed publisher
    ..8, respectively). In addition, the expression of genes involved in ketogenesis (HMGCL) and lipid synthesis (SREBF2, FABP4) was increased in DG, while the expression of ketogenesis (ACAT2, HMGCS) and cholesterol synthesis related ..
  28. Pai J, Brown M, Goldstein J. Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins. Proc Natl Acad Sci U S A. 1996;93:5437-42 pubmed
    ..The current data lend further support to the notion that SREBPs are cleaved and activated as part of the program in programmed cell death...
  29. Lee C, Kong M. An interactive association of common sequence variants in the neuropeptide Y gene with susceptibility to ischemic stroke. Stroke. 2007;38:2663-9 pubmed
    ..variants in 18 candidate genes (ACE, AGT, AGTR1, BDNF, CRP, F13B, LIF, MMP9, NPPA, NPY, PTGS2, SELP, SERPINE1, SREBF2, TFPI, THBD, VCAM1, and VEGF) revealed that NPY might be the most responsible for the susceptibility of ischemic ..
  30. Qiu X, Jin C, Wang W. Association between single nucleotide polymorphisms of sterol regulatory element binding protein-2 gene and risk of knee osteoarthritis in a Chinese Han population. J Int Med Res. 2014;42:320-8 pubmed publisher
    ..SREBP-2 rs2228314 G to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population. ..
  31. Li X, Wu J, Chung L, Huang W. Anti-cancer efficacy of SREBP inhibitor, alone or in combination with docetaxel, in prostate cancer harboring p53 mutations. Oncotarget. 2015;6:41018-32 pubmed publisher
    ..These data suggest for the first time that fatostatin alone or in combination with docetaxel could be exploited as a novel and promising therapy for metastatic PCa harboring p53 mutations. ..
  32. Haskins J, Zhang S, Means R, Kelleher J, Cline G, Canfrán Duque A, et al. Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake. Sci Signal. 2015;8:ra111 pubmed publisher
    ..The connections of EGFR and ERBB4 signaling with SREBP-2-regulated cholesterol metabolism are likely to be important in ERBB-regulated developmental processes and may contribute to metabolic remodeling in ERBB-driven cancers. ..
  33. Assmann N, O Brien K, Donnelly R, Dyck L, Zaiatz Bittencourt V, Loftus R, et al. Srebp-controlled glucose metabolism is essential for NK cell functional responses. Nat Immunol. 2017;18:1197-1206 pubmed publisher
    ..Thus, Srebp controls glucose metabolism in NK cells, and this Srebp-dependent regulation is critical for NK cell effector function. ..
  34. Furuhashi H, Tomita K, Teratani T, Shimizu M, Nishikawa M, Higashiyama M, et al. Vitamin A-coupled liposome system targeting free cholesterol accumulation in hepatic stellate cells offers a beneficial therapeutic strategy for liver fibrosis. Hepatol Res. 2017;: pubmed publisher
    ..free cholesterol (FC) accumulation partly by enhancing signaling via sterol regulatory element-binding protein 2 (SREBP2) and microRNA-33a (miR-33a), which resulted in HSC sensitization to transforming growth factor-? (TGF?)-induced ..
  35. Sato R, Inoue J, Kawabe Y, Kodama T, Takano T, Maeda M. Sterol-dependent transcriptional regulation of sterol regulatory element-binding protein-2. J Biol Chem. 1996;271:26461-4 pubmed
    ..These findings suggest that the activity of SREBP-2 is controlled not only post-translationally by proteolytic activation of the precursor protein but also transcriptionally by itself together with NF-Y. ..
  36. Bell R, Deane R, Chow N, Long X, Sagare A, Singh I, et al. SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells. Nat Cell Biol. 2009;11:143-53 pubmed publisher
    ..Hypoxia stimulated SRF/MYOCD expression in human cerebral VSMCs and in animal models of AD. We suggest that SRF and MYOCD function as a transcriptional switch, controlling Abeta cerebrovascular clearance and progression of AD. ..
  37. Tanaka N, Abe Dohmae S, Iwamoto N, Yokoyama S. Roles of ATP-binding cassette transporter A7 in cholesterol homeostasis and host defense system. J Atheroscler Thromb. 2011;18:274-81 pubmed
    ..impact on the generation of HDL and was found to be associated with phagocytosis regulated by sterol regulatory element binding protein 2. Since phagocytosis is one of the fundamental functions of animal cells as an important ..
  38. Bielicki P, Brzoska K, Pływaczewski R, Barnaś M, Kumor M, Stepkowski T, et al. [Genetic predisposition to ischemic heart disease in patients with obstructive sleep apnea syndrome (OSAS)]. Pol Merkur Lekarski. 2014;36:229-32 pubmed
    ..6%) and twice with GG homozygotes (26.1%). Conclusions. Rating polymorphisms studied genes did not reveal their relationship to the occurrence of IHD in patients with OSAS, both in the whole group as well as separate subgroups. ..
  39. Chandran K, Goswami S, Sharma Walia N. Implications of a peroxisome proliferator-activated receptor alpha (PPARα) ligand clofibrate in breast cancer. Oncotarget. 2016;7:15577-99 pubmed publisher
  40. Malhotra P, Aloman C, Ankireddy A, Khadra H, Ooka K, Gill R, et al. Overactivation of intestinal sterol response element-binding protein 2 promotes diet-induced nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2017;313:G376-G385 pubmed publisher
    ..These data indicate that overactivation of intestinal SREBP2 promotes diet-induced hepatic inflammation with features of human NASH resulting in rapid severe fibrosis and ..
  41. Vaidya H, Gangadaran S, Cheema S. An obesogenic diet enriched with blue mussels protects against weight gain and lowers cholesterol levels in C57BL/6 mice. Nutr Res. 2017;46:31-37 pubmed publisher
    ..In conclusion, our findings have established that BM reduces body weight gain in mice. BM may have potential to lower cholesterol levels by inhibiting cholesterol synthesis, thereby protecting against obesity and perhaps heart disease. ..
  42. Nagoshi E, Imamoto N, Sato R, Yoneda Y. Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip. Mol Biol Cell. 1999;10:2221-33 pubmed
    ..We further demonstrate that the helix-loop-helix-leucine zipper motif of SREBP-2 contains a novel type of nuclear localization signal, which binds directly to importin beta. ..
  43. Liao J, Zhao L, Chen Y, Li Q, Chen Y, Ruan X, et al. [Effect of RNAi-mediated silencing of SREBP2 gene on inflammatory cytokine-induced cholesterol accumulation in HepG2 cells]. Zhonghua Gan Zang Bing Za Zhi. 2012;20:526-31 pubmed publisher
    To investigate the effect of RNA interference (RNAi)-mediated silencing of the SREBP2 on inflammatory cytokine-induced cholesterol accumulation in HepG2 cells...
  44. Yang L, Chen J, Liu D, Yu S, Cong E, Li Y, et al. Association between SREBF2 gene polymorphisms and metabolic syndrome in clozapine-treated patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2015;56:136-41 pubmed publisher
    ..The sterol regulatory element binding transcription factor 2 (SREBF2) gene mainly regulates the cholesterol biosynthetic gene...
  45. Wiersma H, Gatti A, Nijstad N, Kuipers F, Tietge U. Hepatic SR-BI, not endothelial lipase, expression determines biliary cholesterol secretion in mice. J Lipid Res. 2009;50:1571-80 pubmed publisher
    ..05), translating into decreased expression of sterol-regulatory element binding protein 2 (SREBP2) and its target genes HMG-CoA reductase and LDL receptor (each P < 0.01)...
  46. Wang X, Tian Y, Guo Z, Fan Z, Qiu D, Zeng M. Cholesterol metabolism and expression of its relevant genes in cultured steatotic hepatocytes. J Dig Dis. 2009;10:310-4 pubmed publisher
    ..05), whereas the SREBP-2 mRNA was increased only at day 6 (P < 0.05). Cholesterol accumulation is probably due to the upregulated expression of the relevant genes in the cholesterol synthesis of the steatotic hepatocytes. ..
  47. Cui W, Jiang Z, Cai Q, Zhang R, Wu W, Wang J, et al. Decreased NPC1L1 expression in the liver from Chinese female gallstone patients. Lipids Health Dis. 2010;9:17 pubmed publisher
    ..The hepatic NPC1L1 mRNA levels were lower in female GS, correlated with SREBP2 mRNA. NPC1L1 downregulation was confirmed at protein levels...
  48. Aylon Y, Gershoni A, Rotkopf R, Biton I, Porat Z, Koh A, et al. The LATS2 tumor suppressor inhibits SREBP and suppresses hepatic cholesterol accumulation. Genes Dev. 2016;30:786-97 pubmed publisher
    ..A screen for LATS2-interacting proteins in liver-derived cells identified the transcription factor SREBP2, master regulator of cholesterol homeostasis...
  49. Kondo A, Yamamoto S, Nakaki R, Shimamura T, Hamakubo T, Sakai J, et al. Extracellular Acidic pH Activates the Sterol Regulatory Element-Binding Protein 2 to Promote Tumor Progression. Cell Rep. 2017;18:2228-2242 pubmed publisher
    ..8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets, along with intracellular acidification...
  50. Arjuman A, Pandey H, Chandra N. Effect of a combination oral contraceptive (desogestrel+ethinyl estradiol) on the expression of low-density lipoprotein receptor and its transcription factor (SREBP2) in placental trophoblast cells. Contraception. 2011;84:160-8 pubmed publisher
    ..and ethinyl estradiol - on the expression of low-density lipoprotein receptor (LDLR) and its transcription factor (SREBP2) in assessing the functional effectiveness of the LDLR...
  51. Galle M, Kladniew B, Castro M, Villegas S, Lacunza E, Polo M, et al. Modulation by geraniol of gene expression involved in lipid metabolism leading to a reduction of serum-cholesterol and triglyceride levels. Phytomedicine. 2015;22:696-704 pubmed publisher
    ..genes for the low-density-lipoprotein receptor (LDLR), the sterol-regulatory-element-binding transcription factor (SREBF2), the very-low-density-lipoprotein receptor (VLDLR), and the acetyl-CoA carboxylase (ACACA) were determined by ..
  52. Jia L, Song N, Yang G, Ma Y, Li X, Lu R, et al. Effects of Tanshinone IIA on the modulation of miR?33a and the SREBP?2/Pcsk9 signaling pathway in hyperlipidemic rats. Mol Med Rep. 2016;13:4627-35 pubmed publisher
    ..In conclusion, the present study indicated that Tanshinone IIA attenuated lipid deposition in the livers of hyperlipidemic rats and modulated the expression of miR?33a and SREBP?2/Pcsk9 signaling pathway proteins. ..
  53. Dang E, McDonald J, Russell D, Cyster J. Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation. Cell. 2017;171:1057-1071.e11 pubmed publisher
    ..infection or lipopolysaccharide (LPS) stimulation, macrophages upregulate Ch25h to maintain repression of SREBP2 activation and cholesterol synthesis...
  54. Botma G, van Deursen D, Vieira D, van Hoek M, Jansen H, Verhoeven A. Sterol-regulatory-element binding protein inhibits upstream stimulatory factor-stimulated hepatic lipase gene expression. Atherosclerosis. 2005;179:61-7 pubmed
    ..We conclude that the opposite regulation of HL expression by fatty acids and statins is mediated via SREBP, possibly through interaction with USF. ..
  55. 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. ..
  56. Gerin I, Clerbaux L, Haumont O, Lanthier N, Das A, Burant C, et al. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem. 2010;285:33652-61 pubmed publisher
    ..In this study, we provide evidence that the primary transcript of SREBP2 contains an intronic miRNA (miR-33) that reduces cellular cholesterol export via inhibition of translation of the ..
  57. Corral R, Lewinger J, Van Den Berg D, Joshi A, Yuan J, Gago Dominguez M, et al. Comprehensive analyses of DNA repair pathways, smoking and bladder cancer risk in Los Angeles and Shanghai. Int J Cancer. 2014;135:335-47 pubmed publisher
    ..034). The XRCC6 SNP rs2284082 (NHEJ), also in LD with SREBF2, showed an interaction with smoking (smoking status interaction pgene = 0.001, ppathway = 0.008, poverall = 0.034)...
  58. Nagashima S, Morishima K, Okamoto H, Ishibashi S. Possible involvement of PCSK9 overproduction in hyperlipoproteinemia associated with hepatocellular carcinoma: A case report. J Clin Lipidol. 2016;10:1045-1049 pubmed publisher
  59. Vienken H, Mabrouki N, Grabau K, Claas R, Rudowski A, Schömel N, et al. Characterization of cholesterol homeostasis in sphingosine-1-phosphate lyase-deficient fibroblasts reveals a Niemann-Pick disease type C-like phenotype with enhanced lysosomal Ca2+ storage. Sci Rep. 2017;7:43575 pubmed publisher
  60. Landa V, Zidek V, Mlejnek P, Simakova M, Silhavy J, Trnovska J, et al. Sterol regulatory element binding protein 2 overexpression is associated with reduced adipogenesis and ectopic fat accumulation in transgenic spontaneously hypertensive rats. Physiol Res. 2014;63:587-90 pubmed
    It has been reported that the major function of the sterol regulatory element binding protein 2 (SREBP-2) is to activate preferentially cholesterol biosynthesis in liver and adipose tissue rather than fatty acid synthesis...
  61. Hernández Anzaldo S, Brglez V, Hemmeryckx B, Leung D, Filep J, Vance J, et al. Novel Role for Matrix Metalloproteinase 9 in Modulation of Cholesterol Metabolism. J Am Heart Assoc. 2016;5: pubmed
    ..wild-type) mice, Mmp9-/- mice failed to decrease the hepatic expression of sterol regulatory element binding protein 2 pathway genes, which control hepatic cholesterol biosynthesis and uptake...
  62. Ruixing Y, Jinzhen W, Weixiong L, Yuming C, Dezhai Y, Shangling P. The environmental and genetic evidence for the association of hyperlipidemia and hypertension. J Hypertens. 2009;27:251-8 pubmed publisher
    ..These findings suggest that hyperlipidemia and hypertension have many common risk factors. Hyperlipidemia is associated with hypertension in many aspects. ..
  63. Nath S, Chowdhury A, Dey S, Roychoudhury A, Ganguly A, Bhattacharyya D, et al. Deregulation of Rb-E2F1 axis causes chromosomal instability by engaging the transactivation function of Cdc20-anaphase-promoting complex/cyclosome. Mol Cell Biol. 2015;35:356-69 pubmed publisher
    ..We conclude that excess E2F1 due to Rb inactivation recruits the complex of Cdc20 and the anaphase-promoting complex/cyclosome (Cdc20-APC/C) to deregulate the expression of UBCH10, leading to chromosomal instability in cancer cells. ..
  64. Li M, Wang Q, Liu S, Zhang J, Ju W, Quan M, et al. MicroRNA-185-5p mediates regulation of SREBP2 expression by hepatitis C virus core protein. World J Gastroenterol. 2015;21:4517-25 pubmed publisher
    ..The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2 (SREBP2) and the rate-limiting enzyme in cholesterol synthesis (HMGCR) was measured by ..
  65. Li Z, Martin M, Zhang J, Huang H, Bai L, Zhang J, et al. Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility. Circulation. 2017;136:1315-1330 pubmed publisher
    ..Acting as a ligand for liver X receptor (LXR), but an inhibitor of SREBP2 (sterol regulatory element-binding protein 2), 25-hydroxycholesterol, and its catalyzing enzyme cholesterol-25-..
  66. 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. ..
  67. Natesampillai S, Fernandez Zapico M, Urrutia R, Veldhuis J. A novel functional interaction between the Sp1-like protein KLF13 and SREBP-Sp1 activation complex underlies regulation of low density lipoprotein receptor promoter function. J Biol Chem. 2006;281:3040-7 pubmed
  68. Berthold H, Laaksonen R, Lehtimaki T, Gylling H, Krone W, Gouni Berthold I. SREBP-1c gene polymorphism is associated with increased inhibition of cholesterol-absorption in response to ezetimibe treatment. Exp Clin Endocrinol Diabetes. 2008;116:262-7 pubmed
    ..The CC homozygotes have a significantly increased response to the effects of ezetimibe on cholesterol absorption compared to the G allele-carriers, suggesting that SREBP-1 may be implicated in ezetimibe's mechanism of action. ..
  69. Kim Y, Park J, Lee C. Multilocus genotypic association with vascular dementia by multifactor dimensionality reduction and entropy-based estimation. Psychiatr Genet. 2009;19:253-8 pubmed publisher
    ..four-locus candidate model included transforming growth factor-beta1 Pro10Leu, AGT Thr235Met, sterol regulatory element binding protein 2 G34995T, and leukemia inhibitory factor T4524G with TA of 57.13% (P<0.05)...
  70. Irisawa M, Inoue J, Ozawa N, Mori K, Sato R. The sterol-sensing endoplasmic reticulum (ER) membrane protein TRC8 hampers ER to Golgi transport of sterol regulatory element-binding protein-2 (SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2 cleavage. J Biol Chem. 2009;284:28995-9004 pubmed publisher
  71. Prabhu A, Krycer J, Brown A. Overexpression of a key regulator of lipid homeostasis, Scap, promotes respiration in prostate cancer cells. FEBS Lett. 2013;587:983-8 pubmed publisher
    ..This striking observation warrants further investigation. Given that SREBP-2 and Scap are regulated by factors driving prostate growth, exploring this observation further could shed light on prostate carcinogenesis. ..
  72. Ivatt R, Sanchez Martinez A, Godena V, Brown S, Ziviani E, Whitworth A. Genome-wide RNAi screen identifies the Parkinson disease GWAS risk locus SREBF1 as a regulator of mitophagy. Proc Natl Acad Sci U S A. 2014;111:8494-9 pubmed publisher
    ..However, with the recent identification of SREBF1 as a risk locus for sporadic PD, our findings suggest a common mechanistic link between autosomal recessive and sporadic PD, and underscore the importance of mitochondrial homeostasis. ..
  73. Lee S, Sekimoto T, Yamashita E, Nagoshi E, Nakagawa A, Imamoto N, et al. The structure of importin-beta bound to SREBP-2: nuclear import of a transcription factor. Science. 2003;302:1571-5 pubmed
    ..Importin-beta changes its conformation to reveal a pseudo-twofold symmetry on its surface structure so that it can accommodate a symmetric dimer molecule. Importin-beta may use a similar strategy to recognize other dimeric cargoes. ..
  74. Schiavoni G, Bennati A, Castelli M, Della Fazia M, Beccari T, Servillo G, et al. Activation of TM7SF2 promoter by SREBP-2 depends on a new sterol regulatory element, a GC-box, and an inverted CCAAT-box. Biochim Biophys Acta. 2010;1801:587-92 pubmed publisher
    ..A triple mutagenized promoter construct did not have an additive effect. We conclude that, besides the SRE motif, both the inverted CCAAT-box and GC-box2 are essential for full promoter activation by SREBP-2. ..
  75. Ishimoto K, Tachibana K, Hanano I, Yamasaki D, Nakamura H, Kawai M, et al. Sterol-regulatory-element-binding protein 2 and nuclear factor Y control human farnesyl diphosphate synthase expression and affect cell proliferation in hepatoblastoma cells. Biochem J. 2010;429:347-57 pubmed publisher
    ..These results suggest that SREBP-2 and NF-Y are required to trigger cell proliferation through the induction of FDPS expression and that the pharmacological action of zoledronic acid is involved in this pathway. ..
  76. Chen Z, Martin M, Li Z, Shyy J. Endothelial dysfunction: the role of sterol regulatory element-binding protein-induced NOD-like receptor family pyrin domain-containing protein 3 inflammasome in atherosclerosis. Curr Opin Lipidol. 2014;25:339-49 pubmed publisher
    ..Furthermore, targeting SREBP-inflammasome pathways can be a therapeutic strategy for attenuating atherosclerosis. ..
  77. Poletti S, Aggio V, Bollettini I, Falini A, Colombo C, Benedetti F. SREBF-2 polymorphism influences white matter microstructure in bipolar disorder. Psychiatry Res Neuroimaging. 2016;257:39-46 pubmed publisher
    ..These results seem to suggest an involvement of SREBF-2 in the integrity of white matter tracts in BD and therefore a possible role of SREBP pathway in CNS myelination processes. ..
  78. Hsu M, Savas U, Griffin K, Johnson E. Regulation of human cytochrome P450 4F2 expression by sterol regulatory element-binding protein and lovastatin. J Biol Chem. 2007;282:5225-36 pubmed
    ..Collectively, these results demonstrate that SREBPs transactivate CYP4F2 transcription and that CYP4F2 induction by statins is mediated by SREBP-2. ..
  79. Tanaka N, Abe Dohmae S, Iwamoto N, Fitzgerald M, Yokoyama S. HMG-CoA reductase inhibitors enhance phagocytosis by upregulating ATP-binding cassette transporter A7. Atherosclerosis. 2011;217:407-14 pubmed publisher
    ..cassette transporter (ABC) A7 strongly associates with phagocytosis, being regulated by sterol regulatory element binding protein 2. We therefore examined the effect of statins on phagocytosis in vitro and in vivo through the ..
  80. Hager L, Li L, Pun H, Liu L, Hossain M, Maguire G, et al. Lecithin:cholesterol acyltransferase deficiency protects against cholesterol-induced hepatic endoplasmic reticulum stress in mice. J Biol Chem. 2012;287:20755-68 pubmed publisher
    ..in conjunction with decreased hepatic Abcg5/g8 mRNA, increased Npc1l1 mRNA, and decreased Hmgr mRNA and nuclear SREBP2 protein. Intestinal NPC1L1 protein was induced...
  81. Li Y, Xu S, Jiang B, Cohen R, Zang M. Activation of sterol regulatory element binding protein and NLRP3 inflammasome in atherosclerotic lesion development in diabetic pigs. PLoS ONE. 2013;8:e67532 pubmed publisher
    ..These translational studies provide in vivo evidence that the dysregulation of SIRT1-AMPK-SREBP and stimulation of NLRP3 inflammasome may contribute to vascular lipid deposition and inflammation in atherosclerosis...
  82. Shao W, Espenshade P. Sterol regulatory element-binding protein (SREBP) cleavage regulates Golgi-to-endoplasmic reticulum recycling of SREBP cleavage-activating protein (SCAP). J Biol Chem. 2014;289:7547-57 pubmed publisher
    ..However, we show that SREBP actively prevents premature recycling of SCAP-SREBP until initiation of SREBP cleavage. SREBP regulates SCAP in human cells and yeast, indicating that this is an ancient regulatory mechanism. ..
  83. Steen V, Skrede S, Polushina T, López M, Andreassen O, Fernø J, et al. Genetic evidence for a role of the SREBP transcription system and lipid biosynthesis in schizophrenia and antipsychotic treatment. Eur Neuropsychopharmacol. 2017;27:589-598 pubmed publisher
    ..cholesterol is regulated by the sterol regulatory element binding protein (SREBP) transcription factors SREBP1 and SREBP2, which are encoded by the SREBF1 and SREBF2 genes on chromosome 17p11.2 and 22q13.2, respectively...
  84. Lebeau P, Al Hashimi A, Sood S, Lhotak S, Yu P, Gyulay G, et al. Endoplasmic Reticulum Stress and Ca2+ Depletion Differentially Modulate the Sterol Regulatory Protein PCSK9 to Control Lipid Metabolism. J Biol Chem. 2017;292:1510-1523 pubmed publisher
    ..Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER-localized transcription factor that directly up-regulates sterol regulatory genes, including PCSK9 Given ..
  85. Jang J, Park H, Yoo H, Baek I, Yoon J, Ko M, et al. Protective role of endogenous plasmalogens against hepatic steatosis and steatohepatitis in mice. Hepatology. 2017;66:416-431 pubmed publisher
    ..Further study of AG or other agents that increase hepatic plasmalogen levels may identify novel therapeutic strategies against NASH. (Hepatology 2017;66:416-431). ..
  86. Nagoshi E, Yoneda Y. Dimerization of sterol regulatory element-binding protein 2 via the helix-loop-helix-leucine zipper domain is a prerequisite for its nuclear localization mediated by importin beta. Mol Cell Biol. 2001;21:2779-89 pubmed
    ..These results indicate that dimerization is a prerequisite process for the nuclear import of SREBP-2 mediated by importin beta. ..
  87. Vidal H, Mondesert G, Galiegue S, Carrière D, Dupuy P, Carayon P, et al. Identification and pharmacological characterization of SRBP-2: a novel SR31747A-binding protein. Cancer Res. 2003;63:4809-18 pubmed
    ..These findings demonstrated that SRBP-2 represents an additional molecular target for SR31747A, which could help to understand the immunosuppressive and antiproliferative effects of the molecule. ..
  88. van t Wout A, Swain J, Schindler M, Rao U, Pathmajeyan M, Mullins J, et al. Nef induces multiple genes involved in cholesterol synthesis and uptake in human immunodeficiency virus type 1-infected T cells. J Virol. 2005;79:10053-8 pubmed
  89. Zhang P, Liu Y, Guo Y, Miao F, Yu Z, Wang S. [Oxidized low-density lipoprotein enhances the expressions of SREBP-2 and HMGCR mRNA in macrophages derived from the monocytes of patients with acute coronary syndrome]. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29:929-32 pubmed
    ..05). Within a defined dose range, ox-LDL can dose-dependently enhance the expressions of SREBP-2 and HMGCR mRNA in macrophages from patients with ACS. ..
  90. Chen Z, Ding Z, Ma G, Liu N, Qian Q. Sterol regulatory element-binding transcription factor (SREBF)-2, SREBF cleavage-activating protein (SCAP), and premature coronary artery disease in a Chinese population. Mol Biol Rep. 2011;38:2895-901 pubmed publisher
    ..05). We could not identify any association between these two SNPs and premature CAD or extent of coronary lesions in a Chinese population. ..
  91. Wang Y, Tong J, Chang B, Wang B, Zhang D, Wang B. Relationship of SREBP-2 rs2228314 G>C polymorphism with nonalcoholic fatty liver disease in a Han Chinese population. Genet Test Mol Biomarkers. 2014;18:653-7 pubmed publisher
    ..05). The results of this study provide evidence that the GG genotype and G carrier (CG+GG) of rs2228314 G>C polymorphism in the SREBP-2 gene may increase the risk of NAFLD. ..
  92. Chen Z, Wen L, Martin M, Hsu C, Fang L, Lin F, et al. Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a. Circulation. 2015;131:805-14 pubmed publisher
    ..Here, we postulated that oxidative stress induces sterol regulatory element-binding protein 2 (SREBP2) and microRNA-92a (miR-92a), which in turn activate endothelial innate immune response, leading to dysfunctional ..