sterol regulatory element binding proteins


Summary: Sterol regulatory element binding proteins are basic helix-loop-helix leucine zipper transcription factors that bind the sterol regulatory element TCACNCCAC. They are synthesized as precursors that are threaded into the MEMBRANES of the ENDOPLASMIC RETICULUM.

Top Publications

  1. 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
    b>Sterol regulatory element binding proteins (SREBP) are major regulators of fatty acid and cholesterol synthesis...
  2. Blatzer M, Barker B, Willger S, Beckmann N, Blosser S, Cornish E, et al. SREBP coordinates iron and ergosterol homeostasis to mediate triazole drug and hypoxia responses in the human fungal pathogen Aspergillus fumigatus. PLoS Genet. 2011;7:e1002374 pubmed publisher
    b>Sterol regulatory element binding proteins (SREBPs) are a class of basic helix-loop-helix transcription factors that regulate diverse cellular responses in eukaryotes...
  3. Stewart E, Nwosu C, Tong Z, Roguev A, Cummins T, Kim D, et al. Yeast SREBP cleavage activation requires the Golgi Dsc E3 ligase complex. Mol Cell. 2011;42:160-71 pubmed publisher
    ..Together, these data suggest that the Golgi Dsc E3 ligase complex functions in a post-ER pathway for protein degradation. ..
  4. Jeon T, Osborne T. SREBPs: metabolic integrators in physiology and metabolism. Trends Endocrinol Metab. 2012;23:65-72 pubmed publisher
    Recent advances have significantly increased our understanding of how sterol regulatory element binding proteins (SREBPs) are regulated at the transcriptional and post-transcriptional levels in response to cellular signaling...
  5. 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. ..
  6. Brown M, Goldstein J. Cholesterol feedback: from Schoenheimer's bottle to Scap's MELADL. J Lipid Res. 2009;50 Suppl:S15-27 pubmed publisher
    ..In this article we review the major milestones in the cholesterol feedback story. ..
  7. Hughes B, Espenshade P. Oxygen-regulated degradation of fission yeast SREBP by Ofd1, a prolyl hydroxylase family member. EMBO J. 2008;27:1491-501 pubmed publisher
    ..Our data support a model whereby the Ofd1 N-terminal dioxygenase domain is an oxygen sensor that regulates the activity of the C-terminal degradation domain. ..
  8. Rasmussen H, Blobaum K, Park Y, Ehlers S, Lu F, Lee J. Lipid extract of Nostoc commune var. sphaeroides Kutzing, a blue-green alga, inhibits the activation of sterol regulatory element binding proteins in HepG2 cells. J Nutr. 2008;138:476-81 pubmed
    ..05). Therefore, our results demonstrate that N. commune lipid extract inhibits the maturation process of both SREBP-1 and -2, resulting in a decrease in expression of genes involved in cholesterol and fatty acid metabolism. ..
  9. Stewart E, LLOYD S, Burg J, Nwosu C, Lintner R, Daza R, et al. Yeast sterol regulatory element-binding protein (SREBP) cleavage requires Cdc48 and Dsc5, a ubiquitin regulatory X domain-containing subunit of the Golgi Dsc E3 ligase. J Biol Chem. 2012;287:672-81 pubmed publisher

More Information


  1. Dong X, Tang S. Insulin-induced gene: a new regulator in lipid metabolism. Peptides. 2010;31:2145-50 pubmed publisher
    ..In this article, we focus on the functions, expression and regulation, gene polymorphisms of Insigs, and their deficiency with diseases. ..
  2. Willger S, Puttikamonkul S, Kim K, Burritt J, Grahl N, Metzler L, et al. A sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus. PLoS Pathog. 2008;4:e1000200 pubmed publisher
    ..Thus, these findings present a new function of SREBP proteins in filamentous fungi, and demonstrate for the first time that hypoxia adaptation is likely an important virulence attribute of pathogenic molds. ..
  3. Raghow R, Yellaturu C, Deng X, Park E, Elam M. SREBPs: the crossroads of physiological and pathological lipid homeostasis. Trends Endocrinol Metab. 2008;19:65-73 pubmed publisher
  4. Lee P, Liu P, Li W, DeBose Boyd R. Amplification of the gene for SCAP, coupled with Insig-1 deficiency, confers sterol resistance in mutant Chinese hamster ovary cells. J Lipid Res. 2007;48:1944-54 pubmed
    ..These results highlight the importance of SCAP/Insig ratios in normal sterol-regulated processing of SREBPs in cultured cells. ..
  5. Chang Y, Bien C, Lee H, Espenshade P, Kwon Chung K. Sre1p, a regulator of oxygen sensing and sterol homeostasis, is required for virulence in Cryptococcus neoformans. Mol Microbiol. 2007;64:614-29 pubmed
    ..Animal studies confirm the importance of SRE1 for C. neoformans to adapt to the host environment and to cause fatal meningoencephalitis, thereby identifying the SREBP pathway as a therapeutic target for cryptococcosis. ..
  6. Moriishi K, Mochizuki R, Moriya K, Miyamoto H, Mori Y, Abe T, et al. Critical role of PA28gamma in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis. Proc Natl Acad Sci U S A. 2007;104:1661-6 pubmed
    ..These findings suggest that PA28gamma plays a crucial role in the development of liver pathology induced by HCV infection. ..
  7. Ruan X, Moorhead J, Tao J, Ma K, Wheeler D, Powis S, et al. Mechanisms of dysregulation of low-density lipoprotein receptor expression in vascular smooth muscle cells by inflammatory cytokines. Arterioscler Thromb Vasc Biol. 2006;26:1150-5 pubmed
    ..The implication of these findings is that inflammatory cytokines may contribute to intracellular LDL accumulation without previous modification of the lipoprotein. ..
  8. 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. ..
  9. Gong Y, Lee J, Lee P, Goldstein J, Brown M, Ye J. Sterol-regulated ubiquitination and degradation of Insig-1 creates a convergent mechanism for feedback control of cholesterol synthesis and uptake. Cell Metab. 2006;3:15-24 pubmed
    ..When the new Insig-1 and cholesterol converge on Scap, Scap/SREBP binds to Insig-1, preventing ubiquitination. The Insig-1/Scap/SREBP complex accumulates in the ER, ready for liberation when the cell is again sterol deprived. ..
  10. Llorente Cortes V, Royo T, Otero Viñas M, Berrozpe M, Badimon L. Sterol regulatory element binding proteins downregulate LDL receptor-related protein (LRP1) expression and LRP1-mediated aggregated LDL uptake by human macrophages. Cardiovasc Res. 2007;74:526-36 pubmed
    ..The aim of this work was to analyze whether sterol regulatory element binding proteins (SREBPs) modulate LRP1 expression and LRP1-mediated agLDL uptake by human monocyte-derived ..
  11. Hughes A, Lee C, Bien C, Espenshade P. 4-Methyl sterols regulate fission yeast SREBP-Scap under low oxygen and cell stress. J Biol Chem. 2007;282:24388-96 pubmed
  12. Chang Y, Ingavale S, Bien C, Espenshade P, Kwon Chung K. Conservation of the sterol regulatory element-binding protein pathway and its pathobiological importance in Cryptococcus neoformans. Eukaryot Cell. 2009;8:1770-9 pubmed publisher
    ..These findings suggest that the SREBP pathway is highly conserved in C. neoformans and it serves as an important link between sterol biosynthesis, oxygen sensing, CoCl(2) sensitivity, and virulence in C. neoformans. ..
  13. Matthews K, Ozdemir C, Rawson R. Activation of sterol regulatory element binding proteins in the absence of Scap in Drosophila melanogaster. Genetics. 2010;185:189-98 pubmed publisher
    The escort factor Scap is essential in mammalian cells for regulated activation of sterol regulatory element binding proteins (SREBPs). SREBPs are membrane-bound transcription factors. Cells lacking Scap cannot activate SREBP...
  14. Chang M, Yeh C, Chen J, Huang C, Lin S, Sheen I, et al. Altered expression patterns of lipid metabolism genes in an animal model of HCV core-related, nonobese, modest hepatic steatosis. BMC Genomics. 2008;9:109 pubmed publisher
    ..Some genes of lipid metabolism, mitochondrial function, and immune reaction and the SREBP pathway are involved in HCV core-related, nonobese, modest hepatic steatosis. ..
  15. Sun L, Seemann J, Goldstein J, Brown M. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins. Proc Natl Acad Sci U S A. 2007;104:6519-26 pubmed publisher
  16. Oem J, Jackel Cram C, Li Y, Zhou Y, Zhong J, Shimano H, et al. Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2. J Gen Virol. 2008;89:1225-30 pubmed publisher
    ..Taken together, our results suggest that HCV NS2 can upregulate the transcription of SREBP-1c and FAS, and thus is probably a contributing factor for HCV-associated steatosis...
  17. Raeder M, Fernø J, Glambek M, Stansberg C, Steen V. Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells. Neurosci Lett. 2006;395:185-90 pubmed
    ..These results link antidepressant drugs, but not mood-stabilizers, to SREBP-mediated activation of cellular lipogenesis, and demonstrate a functional similarity between antipsychotic and antidepressant molecular drug action. ..
  18. 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
    ..TheSrebf2gene thus provides a useful model to explore the role of alternative polyadenylation in regulating stage-dependent functions of important protein regulators in spermatogenic cells. ..
  19. Sato R. Sterol metabolism and SREBP activation. Arch Biochem Biophys. 2010;501:177-81 pubmed publisher
    ..Sterol metabolites, including cholesterol, 24,25-dihydrolanosterol and oxysterols, strongly participate in the regulation of sterol metabolism via binding to its particular proteins. ..
  20. Bien C, Espenshade P. Sterol regulatory element binding proteins in fungi: hypoxic transcription factors linked to pathogenesis. Eukaryot Cell. 2010;9:352-9 pubmed publisher
    b>Sterol regulatory element binding proteins (SREBPs) are membrane-bound transcription factors whose proteolytic activation is controlled by the cellular sterol concentration...
  21. Motamed M, Zhang Y, Wang M, Seemann J, Kwon H, Goldstein J, et al. Identification of luminal Loop 1 of Scap protein as the sterol sensor that maintains cholesterol homeostasis. J Biol Chem. 2011;286:18002-12 pubmed publisher
    ..These results indicate that luminal Loop 1 of Scap controls the conformation of cytosolic Loop 6, thereby determining whether cells produce cholesterol. ..
  22. Espenshade P. SREBPs: sterol-regulated transcription factors. J Cell Sci. 2006;119:973-6 pubmed
  23. 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
  24. Hawkins J, Robbins M, Warren L, Xia D, Petras S, Valentine J, et al. Pharmacologic inhibition of site 1 protease activity inhibits sterol regulatory element-binding protein processing and reduces lipogenic enzyme gene expression and lipid synthesis in cultured cells and experimental animals. J Pharmacol Exp Ther. 2008;326:801-8 pubmed publisher
  25. Ikonen E. Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol. 2008;9:125-38 pubmed publisher
    ..Increased understanding of these processes and their integration at the organ systems level provides fundamental insights into the physiology of cholesterol trafficking. ..
  26. 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
    ..cells is controlled at the transcriptional level by a homeostatic feedback pathway involving sterol regulatory element binding proteins (SREBPs)...
  27. Hay B, Abrams B, Zumbrunn A, Valentine J, Warren L, Petras S, et al. Aminopyrrolidineamide inhibitors of site-1 protease. Bioorg Med Chem Lett. 2007;17:4411-4 pubmed
    ..The discovery and efficacy of a series of potent aminopyrrolidineamide-based inhibitors of sterol regulatory element binding protein site-1 protease is described. ..
  28. Radhakrishnan A, Ikeda Y, Kwon H, Brown M, Goldstein J. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig. Proc Natl Acad Sci U S A. 2007;104:6511-8 pubmed
    ..These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells. ..
  29. Fernø J, Skrede S, Vik Mo A, Håvik B, Steen V. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs. BMC Neurosci. 2006;7:69 pubmed
    ..We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs. ..
  30. Inoue J, Ito Y, Shimada S, Satoh S, Sasaki T, Hashidume T, et al. Glutamine stimulates the gene expression and processing of sterol regulatory element binding proteins, thereby increasing the expression of their target genes. FEBS J. 2011;278:2739-50 pubmed publisher
    ..the more the expression of genes related to lipid homeostasis is promoted by the activation of sterol regulatory element binding proteins (SREBPs) at the transcriptional and post-translational levels in human hepatoma HepG2 cells...
  31. Kamisuki S, Mao Q, Abu Elheiga L, Gu Z, Kugimiya A, Kwon Y, et al. A small molecule that blocks fat synthesis by inhibiting the activation of SREBP. Chem Biol. 2009;16:882-92 pubmed publisher
    b>Sterol regulatory element binding proteins (SREBPs) are transcription factors that activate transcription of the genes involved in cholesterol and fatty acid biosynthesis...
  32. Ma Y, Li B, Gao H, Yao M, Koch W, Eckhart A, et al. [Activation of sterol regulatory element binding protein and its involvement in endothelial cell migration]. Zhonghua Bing Li Xue Za Zhi. 2009;38:50-4 pubmed
    ..SREBP is activated during and plays a critical role in ECs migration. Targeting SREBP could become a novel approach in fighting diseases involving abnormal ECs migration. ..
  33. Krycer J, Sharpe L, Luu W, Brown A. The Akt-SREBP nexus: cell signaling meets lipid metabolism. Trends Endocrinol Metab. 2010;21:268-76 pubmed publisher
    ..We consider this relationship in diseases where Akt and lipids play crucial roles, including diabetes, viral infections and cancer, suggesting that this Akt-SREBP link provides fresh insights into human health and disease. ..
  34. Di Nunzio M, van Deursen D, Verhoeven A, Bordoni A. n-3 and n-6 Polyunsaturated fatty acids suppress sterol regulatory element binding protein activity and increase flow of non-esterified cholesterol in HepG2 cells. Br J Nutr. 2010;103:161-7 pubmed publisher be related to the regulation of lipid biosynthesis through transcription factors including sterol regulatory element binding proteins (SREBP)...
  35. Morohashi Y, Tomita T. Protein trafficking and maturation regulate intramembrane proteolysis. Biochim Biophys Acta. 2013;1828:2855-61 pubmed publisher
    ..In this review, we will discuss recent advances in our understanding of how each i-CLiP proteolysis is regulated by intracellular vesicle trafficking. This article is part of a Special Issue entitled: Intramembrane Proteases. ..
  36. Passeri M, Cinaroglu A, Gao C, Sadler K. Hepatic steatosis in response to acute alcohol exposure in zebrafish requires sterol regulatory element binding protein activation. Hepatology. 2009;49:443-52 pubmed publisher
    ..Srebp activation is required for steatosis in this model. The tractability of zebrafish genetics provides a valuable tool for dissecting the molecular pathogenesis of acute ALD. ..
  37. Brookheart R, Lee C, Espenshade P. Casein kinase 1 regulates sterol regulatory element-binding protein (SREBP) to control sterol homeostasis. J Biol Chem. 2014;289:2725-35 pubmed publisher
    ..Given the role of mammalian Hhp2 homologs, casein kinase 1? and 1?, in regulation of the circadian clock, these findings may provide a mechanism for coordinating circadian rhythm and lipid metabolism. ..
  38. Worgall T. Sphingolipids: major regulators of lipid metabolism. Curr Opin Clin Nutr Metab Care. 2007;10:149-55 pubmed
    ..Emerging data strongly suggest a role of sphingolipid synthesis in the regulation of transcription factors and regulatory proteins that control cellular lipid homeostasis. ..
  39. Piccinetti C, Migliarini B, Olivotto I, Simoniello M, Giorgini E, Carnevali O. Melatonin and peripheral circuitries: insights on appetite and metabolism in Danio rerio. Zebrafish. 2013;10:275-82 pubmed publisher
    ..The findings obtained in this study could be of great interest for a better understanding of the molecular mechanisms as the basis of food intake control and, in turn, can be a useful tool for medical and aquaculture applications...
  40. Yuan Y, Li P, Ye J. Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis. Protein Cell. 2012;3:173-81 pubmed publisher
    ..Understanding the process of foam cell formation will aid in the future discovery of novel therapeutic interventions for atherosclerosis...
  41. Vassas T, Burghardt K, Ellingrod V. Pharmacogenomics of sterol synthesis and statin use in schizophrenia subjects treated with antipsychotics. Pharmacogenomics. 2014;15:61-7 pubmed publisher
    ..Future investigations may allow for personalizing dyslipidemia treatment based on pharmacogenetics within schizophrenia. ..
  42. Syed G, Tang H, Khan M, Hassanein T, Liu J, Siddiqui A. Hepatitis C virus stimulates low-density lipoprotein receptor expression to facilitate viral propagation. J Virol. 2014;88:2519-29 pubmed publisher
    ..Abrogation of HCV-mediated upregulation of LDLR inhibits serum lipid uptake and thereby perturbs HCV replication. Overall, our findings highlight the importance of serum lipid uptake by infected hepatocytes in HCV life cycle. ..
  43. Caruana B, Skoric A, Brown A, Lutze Mann L. Site-1 protease, a novel metabolic target for glioblastoma. Biochem Biophys Res Commun. 2017;490:760-766 pubmed publisher
    b>Sterol regulatory element binding proteins (SREBPs) are transcriptional regulators of lipids which promote glioblastoma growth. Here, we investigate the effect of inhibiting expression of SREBP target genes in human glioblastoma cells...
  44. Tamasawa N. [Disorder of cholesterol metabolism: regulation of intracellular cholesterol and membrane trafficking]. Rinsho Byori. 2010;58:1203-10 pubmed
    ..It will be clarified in the near future disorders of membrane cholesterol trafficking contribute to the pathogeneses of many kinds of disease affecting through ER functioning. ..
  45. Liu X, Li G, Zhu H, Huang L, Liu Y, Ma C, et al. Beneficial effect of berberine on hepatic insulin resistance in diabetic hamsters possibly involves in SREBPs, LXR? and PPAR? transcriptional programs. Endocr J. 2010;57:881-93 pubmed
    ..These results suggest that altered hepatic SREBPs, LXR? and PPAR? transcriptional programs possibly involve in the therapeutic mechanisms of berberine on FIHIR in type 2 diabetic hamsters. ..
  46. Kim H, Okubo T, Juneja L, Yokozawa T. The protective role of amla (Emblica officinalis Gaertn.) against fructose-induced metabolic syndrome in a rat model. Br J Nutr. 2010;103:502-12 pubmed publisher
    ..5 and 10.2 % at the doses of 10 and 20 mg/kg body weight per d, respectively. These findings suggest that fructose-induced metabolic syndrome is attenuated by the polyphenol-rich fraction of amla...
  47. Kang Q, Chen A. Curcumin suppresses expression of low-density lipoprotein (LDL) receptor, leading to the inhibition of LDL-induced activation of hepatic stellate cells. Br J Pharmacol. 2009;157:1354-67 pubmed publisher
    ..This curcumin, a constituent of turmeric, may be useful in preventing hypercholesterolemia-associated hepatic fibrogenesis. ..
  48. Mansilla M, Banchio C, de Mendoza D. Signalling pathways controlling fatty acid desaturation. Subcell Biochem. 2008;49:71-99 pubmed publisher
    ..Here, we review recently discovered components and mechanisms of the regulatory machinery governing the transcription of fatty acid desaturases in bacteria, yeast and animals. ..
  49. Yamauchi Y, Furukawa K, Hamamura K, Furukawa K. Positive feedback loop between PI3K-Akt-mTORC1 signaling and the lipogenic pathway boosts Akt signaling: induction of the lipogenic pathway by a melanoma antigen. Cancer Res. 2011;71:4989-97 pubmed publisher
    ..We thus propose a positive feedback circuit in which PI3K-Akt-mTORC1-SREBP signaling boosts Akt signaling in human melanoma cells expressing GD3. ..
  50. Hampton R. A cholesterol toggle switch. Cell Metab. 2008;8:451-3 pubmed publisher
    ..Work in this issue (Radhakrishnan et al., 2008) employing direct measurement of endoplasmic reticulum cholesterol levels offers insights into the "switch" that controls this system with surprising precision. ..
  51. Andrews D, Schwimmer J, Lavine J. Fast break on the fat brake: mechanism of peroxisome proliferator-activated receptor-delta regulation of lipid accumulation in hepatocytes. Hepatology. 2008;48:355-7 pubmed publisher
  52. Lee M, Puthumana J, Lee S, Kang H, Park J, Jeong C, et al. BDE-47 induces oxidative stress, activates MAPK signaling pathway, and elevates de novo lipogenesis in the copepod Paracyclopina nana. Aquat Toxicol. 2016;181:104-112 pubmed publisher
    ..nana. This study will provide a better understanding of how BDE-47 effects on marine invertebrates particularly on the copepods, an important link in the marine food chain. ..
  53. Chung M, Kang A, Park S, Park K, Jun H, Lee S. The effect of essential oils of dietary wormwood (Artemisia princeps), with and without added vitamin E, on oxidative stress and some genes involved in cholesterol metabolism. Food Chem Toxicol. 2007;45:1400-9 pubmed
    ..such as the LDL receptor, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and sterol regulatory element binding proteins. The induction was increased up to twofold at 0.05 mg/mL of EO treatment in HepG2 cells for 24h...