Gene Symbol: Srebf2
Description: sterol regulatory element binding transcription factor 2
Alias: SREBP-2, SREBP2, Srebf2_retired, sterol regulatory element-binding protein 2, sterol regulatory element binding factor 2
Species: rat
Products:     Srebf2

Top Publications

  1. Ringseis R, Rauer C, Rothe S, Gessner D, Schütz L, Luci S, et al. Sterol regulatory element-binding proteins are regulators of the NIS gene in thyroid cells. Mol Endocrinol. 2013;27:781-800 pubmed publisher
    ..These findings show that TSH acts as a regulator of SREBP expression and maturation in thyroid epithelial cells and that SREBPs are novel transcriptional regulators of NIS. ..
  2. Repa J, Liang G, Ou J, Bashmakov Y, Lobaccaro J, Shimomura I, et al. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev. 2000;14:2819-30 pubmed
    ..Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis, our results reveal a unique regulatory interplay between cholesterol and fatty acid metabolism. ..
  3. Engelking L, Liang G, Hammer R, Takaishi K, Kuriyama H, Evers B, et al. Schoenheimer effect explained--feedback regulation of cholesterol synthesis in mice mediated by Insig proteins. J Clin Invest. 2005;115:2489-98 pubmed
    ..These studies indicate that the essential elements of the regulatory pathway for lipid synthesis function in liver as they do in cultured cells. ..
  4. 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
  5. Jiang P, Gan M, Lin W, Yen S. Nutrient deprivation induces α-synuclein aggregation through endoplasmic reticulum stress response and SREBP2 pathway. Front Aging Neurosci. 2014;6:268 pubmed publisher
    ..enhanced α-syn aggregations concomitant with significant increase of apoptosis as well as ER stress response, SREBP2 activation and cholesterolgenesis...
  6. Boizard M, Le Liepvre X, Lemarchand P, Foufelle F, Ferre P, Dugail I. Obesity-related overexpression of fatty-acid synthase gene in adipose tissue involves sterol regulatory element-binding protein transcription factors. J Biol Chem. 1998;273:29164-71 pubmed
    ..In contrast, immunoreactive SREBP2, which was very low in nuclear extracts from lean rats, was induced in obese rat fat cells...
  7. Ma K, Liu J, Wang C, Ni J, Zhang Y, Wu Y, et al. Activation of mTOR modulates SREBP-2 to induce foam cell formation through increased retinoblastoma protein phosphorylation. Cardiovasc Res. 2013;100:450-60 pubmed publisher
    ..Increased mTORC1 activity was found to up-regulate SREBP-2-mediated cholesterol uptake through Rb phosphorylation. ..
  8. Freed Pastor W, Prives C. Mutant p53: one name, many proteins. Genes Dev. 2012;26:1268-86 pubmed publisher
    ..Here we review mechanisms by which mutant p53 exerts its cellular effects, with a particular focus on the burgeoning mutant p53 transcriptome, and discuss the biological and clinical consequences of mutant p53 gain of function. ..
  9. Amemiya Kudo M, Oka J, Ide T, Matsuzaka T, Sone H, Yoshikawa T, et al. Sterol regulatory element-binding proteins activate insulin gene promoter directly and indirectly through synergy with BETA2/E47. J Biol Chem. 2005;280:34577-89 pubmed
    ..This cryptic SREBP-1c action might play a compensatory role in insulin expression in diabetes with beta cell lipotoxicity. ..

More Information


  1. Tamehiro N, Shigemoto Mogami Y, Kakeya T, Okuhira K, Suzuki K, Sato R, et al. Sterol regulatory element-binding protein-2- and liver X receptor-driven dual promoter regulation of hepatic ABC transporter A1 gene expression: mechanism underlying the unique response to cellular cholesterol status. J Biol Chem. 2007;282:21090-9 pubmed
    ..We conclude that the dual promoter system driven by SREBP-2 and LXR regulates hepatic ABCA1 expression and may mediate the unique response of hepatic ABCA1 gene expression to cellular cholesterol status...
  2. Jiang T, Liebman S, Lucia M, Li J, Levi M. Role of altered renal lipid metabolism and the sterol regulatory element binding proteins in the pathogenesis of age-related renal disease. Kidney Int. 2005;68:2608-20 pubmed
  3. Wang Z, Jiang T, Li J, Proctor G, McManaman J, Lucia S, et al. Regulation of renal lipid metabolism, lipid accumulation, and glomerulosclerosis in FVBdb/db mice with type 2 diabetes. Diabetes. 2005;54:2328-35 pubmed
  4. Xu G, Muller O, Stange E, Fuchs M. Impaired regulation of sterol regulatory element binding protein 2 in cholesterol gallstone-susceptible mice. Biochim Biophys Acta. 2004;1688:274-9 pubmed
    ..Lipid synthesis is under tight transcriptional control involving sterol regulatory element binding proteins (SREBP1, SREBP2)...
  5. Kang Q, Chen A. Curcumin inhibits srebp-2 expression in activated hepatic stellate cells in vitro by reducing the activity of specificity protein-1. Endocrinology. 2009;150:5384-94 pubmed publisher
    ..These results provide novel insights into molecular mechanisms by which curcumin inhibits LDL-induced HSC activation. ..
  6. 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...
  7. Sone H, Shimano H, Sakakura Y, Inoue N, Amemiya Kudo M, Yahagi N, et al. Acetyl-coenzyme A synthetase is a lipogenic enzyme controlled by SREBP-1 and energy status. Am J Physiol Endocrinol Metab. 2002;282:E222-30 pubmed
    ..However, its high conservation among different species and the wide range of its tissue distribution suggest that this enzyme might also play an important role in basic cellular energy metabolism. ..
  8. Ishikawa M, Iwasaki Y, Yatoh S, Kato T, Kumadaki S, Inoue N, et al. Cholesterol accumulation and diabetes in pancreatic beta-cell-specific SREBP-2 transgenic mice: a new model for lipotoxicity. J Lipid Res. 2008;49:2524-34 pubmed publisher
  9. 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. ..
  10. Marseille Tremblay C, Ethier Chiasson M, Forest J, Giguère Y, Masse A, Mounier C, et al. Impact of maternal circulating cholesterol and gestational diabetes mellitus on lipid metabolism in human term placenta. Mol Reprod Dev. 2008;75:1054-62 pubmed
    ..In conclusion, our study suggests that in placenta, expressions of key proteins involved in de novo lipid synthesis are affected by changes in maternal metabolism (HC and GDM) that may subsequently affect fetal development. ..
  11. 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. ..
  12. MacLean P, Vadlamudi S, MacDonald K, Pories W, Barakat H. Suppression of hepatic cholesteryl ester transfer protein expression in obese humans with the development of type 2 diabetes mellitus. J Clin Endocrinol Metab. 2005;90:2250-8 pubmed
    ..Thus, the suppressive effects of type 2 diabetes in obese subjects are observed in both men and women and may be due, at least in part, to a suppression of hepatic CETP expression. ..
  13. Jiang T, Liebman S, Lucia M, Phillips C, Levi M. Calorie restriction modulates renal expression of sterol regulatory element binding proteins, lipid accumulation, and age-related renal disease. J Am Soc Nephrol. 2005;16:2385-94 pubmed
  14. 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. ..
  15. Ryan J, Booth C. Endometriosis of the ureter. Br J Urol. 1992;69:430-1 pubmed
  16. Lopez D, Abisambra Socarrás J, Bedi M, Ness G. Activation of the hepatic LDL receptor promoter by thyroid hormone. Biochim Biophys Acta. 2007;1771:1216-25 pubmed
    ..These results indicate that the rapid induction of the hepatic LDL receptor by thyroid hormone is likely due to direct interaction with TREs rather than indirectly by a mechanism involving SREBP-2. ..
  17. Botolin D, Jump D. Selective proteolytic processing of rat hepatic sterol regulatory element binding protein-1 (SREBP-1) and SREBP-2 during postnatal development. J Biol Chem. 2003;278:6959-62 pubmed
    ..This mechanism differs from the hormonal and fatty acid-mediated pre-translational control of SREBP-1c in adult liver. ..
  18. Osborne T, Espenshade P. Evolutionary conservation and adaptation in the mechanism that regulates SREBP action: what a long, strange tRIP it's been. Genes Dev. 2009;23:2578-91 pubmed publisher
    ..This review integrates classic features of the SREBP pathway with newer information regarding the regulation and sensing mechanisms that serve to assimilate different cellular physiologic processes for optimal function and growth. ..
  19. Wang H, Liu F, Millette C, Kilpatrick D. Expression of a novel, sterol-insensitive form of sterol regulatory element binding protein 2 (SREBP2) in male germ cells suggests important cell- and stage-specific functions for SREBP targets during spermatogenesis. Mol Cell Biol. 2002;22:8478-90 pubmed
    ..Here, we have characterized a novel isoform of the transcription factor SREBP2, which is highly enriched in rat and mouse spermatogenic cells...
  20. Mastrocola R, Guglielmotto M, Medana C, Catalano M, Cutrupi S, Borghi R, et al. Dysregulation of SREBP2 induces BACE1 expression. Neurobiol Dis. 2011;44:116-24 pubmed publisher
    ..In the current study the neuronal activation status of sterol regulatory element binding protein 2 (SREBP2) as well as its involvement in ?-secretase BACE1 activity was investigated in high-fat ..
  21. Wen G, Eder K, Ringseis R. Sterol regulatory element-binding proteins are transcriptional regulators of the thyroglobulin gene in thyroid cells. Biochim Biophys Acta. 2016;1859:994-1003 pubmed publisher
    ..This moreover suggests that SREBP may be molecular targets for pharmacological modulation of TH synthesis. ..
  22. Wang H, Sartini B, Millette C, Kilpatrick D. A developmental switch in transcription factor isoforms during spermatogenesis controlled by alternative messenger RNA 3'-end formation. Biol Reprod. 2006;75:318-23 pubmed
    ..During spermatogenesis, SREBF2 precursor transcripts predominate in premeiotic stages, while SREBF2_v1 is highly upregulated specifically in ..
  23. Xu J, Cho H, O MALLEY S, Park J, Clarke S. Dietary polyunsaturated fats regulate rat liver sterol regulatory element binding proteins-1 and -2 in three distinct stages and by different mechanisms. J Nutr. 2002;132:3333-9 pubmed
    ..These data indicate that PUFA suppress the in vivo proteolytic release of SREBP-1 and -2, but the effect on SREBP-2 is transitory, possibly reflecting the ability of PUFA to enhance cholesterol losses via bile acid synthesis. ..
  24. Ettinger S, Sobel R, Whitmore T, Akbari M, Bradley D, Gleave M, et al. Dysregulation of sterol response element-binding proteins and downstream effectors in prostate cancer during progression to androgen independence. Cancer Res. 2004;64:2212-21 pubmed
    ..As the AI phenotype emerges, enzymes critical for lipogenesis and cholesterol synthesis are activated and likely contribute significantly to cell survival of AI prostate cancer. ..
  25. Lacasa D, Le Liepvre X, Ferre P, Dugail I. Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue. J Biol Chem. 2001;276:11512-6 pubmed
    ..In preadipocytes, progesterone increased ADD1/SREBP1c mRNA dose-dependently, but not SREBP1a or SREBP2. Run-on experiments demonstrated that progesterone action on ADD1/SREBP1c was primarily at the transcriptional ..
  26. Koch A, König B, Spielmann J, Leitner A, Stangl G, Eder K. Thermally oxidized oil increases the expression of insulin-induced genes and inhibits activation of sterol regulatory element-binding protein-2 in rat liver. J Nutr. 2007;137:2018-23 pubmed
  27. 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. ..
  28. Kato T, Shimano H, Yamamoto T, Yokoo T, Endo Y, Ishikawa M, et al. Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice. Cell Metab. 2006;4:143-54 pubmed
    ..Collectively, our data provide evidence that activation of the SREBP-1c/granuphilin pathway is a potential mechanism for impaired insulin secretion in diabetes, contributing to beta cell lipotoxicity. ..
  29. Proctor G, Jiang T, Iwahashi M, Wang Z, Li J, Levi M. Regulation of renal fatty acid and cholesterol metabolism, inflammation, and fibrosis in Akita and OVE26 mice with type 1 diabetes. Diabetes. 2006;55:2502-9 pubmed
  30. Cho E, Yokozawa T, Okamoto T. Protective effect of Chinese prescription Kangen-karyu and its crude drug Tanjin against age-related lipidosis in rats. J Pharm Pharmacol. 2007;59:687-94 pubmed
    ..Evidence has been provided for the anti-ageing activity of Kangen-karyu and its crude drug Tanjin against age-related lipidosis. ..
  31. 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. ..
  32. Kim Y, Nam Y, Lee C. Analysis of the SREBF2 gene as a genetic risk factor for vascular dementia. Am J Med Genet B Neuropsychiatr Genet. 2005;139B:19-22 pubmed
    ..vascular dementia and the polymorphisms of the human gene encoding sterol regulatory element binding protein-2 (SREBF2) that regulates cholesterol metabolism...
  33. Zeng L, Liao H, Liu Y, Lee T, Zhu M, Wang X, et al. Sterol-responsive element-binding protein (SREBP) 2 down-regulates ATP-binding cassette transporter A1 in vascular endothelial cells: a novel role of SREBP in regulating cholesterol metabolism. J Biol Chem. 2004;279:48801-7 pubmed
    ..of cholesterol efflux from cells to apolipoproteins, whereas sterol-responsive element-binding protein 2 (SREBP2) is the key protein regulating cholesterol synthesis and uptake...
  34. Mallampalli R, Ryan A, Carroll J, Osborne T, Thomas C. Lipid deprivation increases surfactant phosphatidylcholine synthesis via a sterol-sensitive regulatory element within the CTP:phosphocholine cytidylyltransferase promoter. Biochem J. 2002;362:81-8 pubmed
    ..These observations indicate that sterol-regulated expression of CCT is mediated by an SRE within its 5' flanking region. ..
  35. Chmielewski M, Sucajtys Szulc E, Kossowska E, Swierczynski J, Rutkowski B, Boguslawski W. Increased gene expression of liver SREBP-2 in experimental chronic renal failure. Atherosclerosis. 2007;191:326-32 pubmed
    ..Enhanced cholesterol synthesis and decreased LDL-receptor mRNA level are probably responsible for an almost fourfold increase in serum cholesterol concentration in CRF rats. ..
  36. Muller P, Miserez A. Identification of mutations in the gene encoding sterol regulatory element binding protein (SREBP)-2 in hypercholesterolaemic subjects. J Med Genet. 2002;39:271-5 pubmed
    ..In summary, this is the first report of mutations in the human SREBP-2 gene to suggest that these and/or other mutations in this key regulator of cholesterol metabolism are associated with hypercholesterolaemia. ..
  37. Rauer C, Ringseis R, Rothe S, Wen G, Eder K. Sterol regulatory element-binding proteins are regulators of the rat thyroid peroxidase gene in thyroid cells. PLoS ONE. 2014;9:e91265 pubmed publisher
    ..In connection with recent findings that the rat NIS gene is also a SREBP target gene in the thyroid, the present findings suggest that SREBPs may be possible novel targets for pharmacological modulation of thyroid hormone synthesis. ..
  38. Matsuda H, Sato M, Yakushiji M, Koshiguchi M, Hirai S, Egashira Y. Regulation of rat hepatic α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase, a key enzyme in the tryptophan- NAD pathway, by dietary cholesterol and sterol regulatory element-binding protein-2. Eur J Nutr. 2014;53:469-77 pubmed
    ..These results provide the first evidence that ACMSD is associated with cholesterol metabolism, and ACMSD gene expression may be upregulated by SREBP-2. ..
  39. Wu J, Zhu Y, Patel S. Cyclosporin-induced dyslipoproteinemia is associated with selective activation of SREBP-2. Am J Physiol. 1999;277:E1087-94 pubmed
  40. 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...
  41. Muller P, Vousden K. p53 mutations in cancer. Nat Cell Biol. 2013;15:2-8 pubmed publisher
    ..Here we highlight some of the emerging molecular mechanisms through which mutant p53 proteins can exert these oncogenic functions. ..
  42. Kim J, Ong W. Localization of the transcription factor, sterol regulatory element binding protein-2 (SREBP-2) in the normal rat brain and changes after kainate-induced excitotoxic injury. J Chem Neuroanat. 2009;37:71-7 pubmed publisher
    ..Taken together, the above results show that there is high level of SREBP-2 expression in the normal hippocampus, and that neuronal injury results in a significant reduction of SREBP-2 expression in the damaged areas. ..
  43. Kim C, Kim H, Mitsuhashi M, Vaziri N. Hepatic tissue sterol regulatory element binding protein 2 and low-density lipoprotein receptor in nephrotic syndrome. Metabolism. 2007;56:1377-82 pubmed
    ..A (HMG-CoA) reductase, and several other cholesterol-regulatory factors is regulated by sterol regulatory element binding protein 2 (SREBP-2)...
  44. Hirayama T, Honda A, Matsuzaki Y, Miyazaki T, Ikegami T, Doy M, et al. Hypercholesterolemia in rats with hepatomas: increased oxysterols accelerate efflux but do not inhibit biosynthesis of cholesterol. Hepatology. 2006;44:602-11 pubmed
    ..Overexpression of the SREBP processing system contributed to the activation of LXRalpha by maintaining high oxysterol levels in tissue...
  45. Boone L, Niesen M, Jaroszeski M, Ness G. In vivo identification of promoter elements and transcription factors mediating activation of hepatic HMG-CoA reductase by T3. Biochem Biophys Res Commun. 2009;385:466-71 pubmed publisher
    ..These data provide in vivo evidence for functional roles for USF-2, SREBP-2, and NF-Y in mediating the T3-induction of hepatic HMGR transcription. ..
  46. Roglans N, Peris C, Verd J, Alegret M, Vazquez M, Sanchez R, et al. Increase in hepatic expression of SREBP-2 by gemfibrozil administration to rats. Biochem Pharmacol. 2001;62:803-9 pubmed
    ..An early increase in the transcriptional activity of SREBP-2 elicited by gemfibrozil administration might be responsible for the observed changes in HMG-CoA reductase, phosphatidate phosphohydrolase, and SREBP-2 expression. ..
  47. Jia Y, Xu R, Sun J, Tang Y, Li J. Enhanced circulating PCSK9 concentration by berberine through SREBP-2 pathway in high fat diet-fed rats. J Transl Med. 2014;12:103 pubmed publisher
  48. Kojima M, Degawa M. Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: correlation with development of hypercholesterolemia. J Appl Toxicol. 2006;26:381-4 pubmed
  49. Pallottini V, Martini C, Cavallini G, Donati A, Bergamini E, Notarnicola M, et al. Modified HMG-CoA reductase and LDLr regulation is deeply involved in age-related hypercholesterolemia. J Cell Biochem. 2006;98:1044-53 pubmed
    ..The SREBP-2 in particular seems to be committed in multiple way to gene transcription. The obtained data represent a good contribution to explain the age-related hypercholesterolemia. ..
  50. Kim H, Vaziri N. Sterol regulatory element-binding proteins, liver X receptor, ABCA1 transporter, CD36, scavenger receptors A1 and B1 in nephrotic kidney. Am J Nephrol. 2009;29:607-14 pubmed publisher
    ..Cellular lipid homeostasis is regulated by the influx, synthesis and efflux of lipids...