Genomes and Genes
sterol regulatory element binding protein 2
Summary: A sterol regulatory element binding protein that regulates GENES involved in CHOLESTEROL synthesis and uptake.
- 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..This may reflect unique roles for cholesterol synthesis and other functional targets of SREBPs during spermatogenesis. ..
- Krycer J, Phan L, Brown A. A key regulator of cholesterol homoeostasis, SREBP-2, can be targeted in prostate cancer cells with natural products. Biochem J. 2012;446:191-201 pubmed publisher..Lastly, androgen-dependent and -independent LNCaP cells were both sensitive to tocotrienols. Overall, this suggests that tocotrienols and other drugs targeting the SREBP-2 pathway are a potential therapeutic option for prostate cancer. ..
- Liang G, Yang J, Horton J, Hammer R, Goldstein J, Brown M. Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. J Biol Chem. 2002;277:9520-8 pubmed..Moreover, these mRNAs, as well as multiple other lipogenic mRNAs, showed a markedly blunted response to the LXR agonist T090137, indicating an essential role of SREBP-1c in the LXR response. ..
- Logette E, Le Jossic Corcos C, Masson D, Solier S, Sequeira Legrand A, Dugail I, et al. Caspase-2, a novel lipid sensor under the control of sterol regulatory element binding protein 2. Mol Cell Biol. 2005;25:9621-31 pubmed
- 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. ..
- 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. ..
- Bensinger S, Bradley M, Joseph S, Zelcer N, Janssen E, Hausner M, et al. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell. 2008;134:97-111 pubmed publisher..These results implicate LXR signaling in a metabolic checkpoint that modulates cell proliferation and immunity. ..
- Zhou R, Yao M, Lee T, Zhu Y, Martins Green M, Shyy J. Vascular endothelial growth factor activation of sterol regulatory element binding protein: a potential role in angiogenesis. Circ Res. 2004;95:471-8 pubmed..SREBP inhibition also markedly suppressed VEGF-induced angiogenesis in chick embryos. In summary, this study identifies SREBPs as the key molecules in regulating angiogenesis in response to VEGF. ..
- 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. ..
- Shechter I, Dai P, Huo L, Guan G. IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells: evidence that IDH1 may regulate lipogenesis in hepatic cells. J Lipid Res. 2003;44:2169-80 pubmed..These results indicate that IDH1 activity is coordinately regulated with the cholesterol and fatty acid biosynthetic pathways and suggest that it is the source for the cytosolic NADPH required by these pathways. ..
- Jeon T, Osborne T. SREBPs: metabolic integrators in physiology and metabolism. Trends Endocrinol Metab. 2012;23:65-72 pubmed publisher..This review focuses on recent advances and new roles for mammalian SREBPs in physiology and metabolism. ..
- Lin T, Zeng L, Liu Y, DeFea K, Schwartz M, Chien S, et al. Rho-ROCK-LIMK-cofilin pathway regulates shear stress activation of sterol regulatory element binding proteins. Circ Res. 2003;92:1296-304 pubmed..By enhancing the SREBP-mediated cholesterol metabolism, this unique mechanism may contribute to endothelial cell functions under flow. ..
- Giandomenico V, Simonsson M, Grönroos E, Ericsson J. Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors. Mol Cell Biol. 2003;23:2587-99 pubmed..Thus, our studies define acetylation-dependent stabilization of transcription factors as a novel mechanism for coactivators to regulate gene expression. ..
- Assaf S, Hazard D, Pitel F, Morisson M, Alizadeh M, Gondret F, et al. Cloning of cDNA encoding the nuclear form of chicken sterol response element binding protein-2 (SREBP-2), chromosomal localization, and tissue expression of chicken SREBP-1 and -2 genes. Poult Sci. 2003;82:54-61 pubmed..However, unlike SREBP-2, SREBP-1 is expressed preferentially in the liver and uropygial gland, suggesting an important role of SREBP-1 in the regulation of lipogenesis in avian species. ..
- Colgan S, Hashimi A, Austin R. Endoplasmic reticulum stress and lipid dysregulation. Expert Rev Mol Med. 2011;13:e4 pubmed publisher..This review will provide an overview of ER stress and the UPR as well as cholesterol homeostasis and SREBP regulation, with an emphasis on their interaction and biological relevance. ..
- Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T, Nagao K, et al. MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo. Proc Natl Acad Sci U S A. 2010;107:17321-6 pubmed publisher..Moreover, miR-33-deficient mice had significantly higher serum HDL cholesterol levels than WT mice. These data establish a critical role for miR-33 in the regulation of ABCA1 expression and HDL biogenesis in vivo...
- Spencer C, Schafer X, Moorman N, Munger J. Human cytomegalovirus induces the activity and expression of acetyl-coenzyme A carboxylase, a fatty acid biosynthetic enzyme whose inhibition attenuates viral replication. J Virol. 2011;85:5814-24 pubmed publisher..These findings indicate that HCMV infection actively modulates numerous functional aspects of a key metabolic regulatory enzyme that is important for high-titer viral replication. ..
- Luu W, Sharpe L, Stevenson J, Brown A. Akt acutely activates the cholesterogenic transcription factor SREBP-2. Biochim Biophys Acta. 2012;1823:458-64 pubmed publisher..Together, this study provides compelling evidence that Akt contributes to the acute regulation of cholesterol metabolism through activating sterol-regulatory element binding protein-2. ..
- Min H, Kapoor A, Fuchs M, Mirshahi F, Zhou H, Maher J, et al. Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease. Cell Metab. 2012;15:665-74 pubmed publisher..HMGCR expression was correlated with FC, histologic severity of NAFLD and LDL-cholesterol. These data demonstrate dysregulated cholesterol metabolism in NAFLD which may contribute to disease severity and cardiovascular risks. ..
- Baselga Escudero L, Arola Arnal A, Pascual Serrano A, Ribas Latre A, Casanova E, Salvadó M, et al. Chronic administration of proanthocyanidins or docosahexaenoic acid reverses the increase of miR-33a and miR-122 in dyslipidemic obese rats. PLoS ONE. 2013;8:e69817 pubmed publisher..These findings cast new light on the regulation of miR-33a and miR-122 in a dyslipidemic model of obese rats and the way these miRNAs are modulated by dietary components in the liver and in PBMCs. ..
- Iwamoto N, Abe Dohmae S, Sato R, Yokoyama S. ABCA7 expression is regulated by cellular cholesterol through the SREBP2 pathway and associated with phagocytosis. J Lipid Res. 2006;47:1915-27 pubmed..We conclude that the ABCA7 gene is regulated by sterol in the opposite direction to ABCA1 through SRE/SREBP2 and that expression of ABCA7 by this regulation is associated with phagocytic activity...
- Zeng L, Lu M, Mori K, Luo S, Lee A, Zhu Y, et al. ATF6 modulates SREBP2-mediated lipogenesis. EMBO J. 2004;23:950-8 pubmed..As a functional consequence, the lipogenic effect of SREBP2(N) in liver cells was suppressed by ATF6(N). Our results provide a novel mechanism by which ATF6 antagonizes SREBP2 to regulate the homeostasis of lipid and glucose. ..
- Kim H, Kim J, Kim J, Park S, Seo J, Kim J, et al. Differential regulation of human and mouse orphan nuclear receptor small heterodimer partner promoter by sterol regulatory element binding protein-1. J Biol Chem. 2004;279:28122-31 pubmed..We propose a possible role of SREBP-1 in the species differential regulation of cholesterol and bile acid homeostasis via a novel mechanism of up-regulation of the hSHP gene expression. ..
- 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. ..
- Swinnen J, Heemers H, Van de Sande T, de Schrijver E, Brusselmans K, Heyns W, et al. Androgens, lipogenesis and prostate cancer. J Steroid Biochem Mol Biol. 2004;92:273-9 pubmed
- Lim K, Chang H. O-GlcNAc inhibits interaction between Sp1 and sterol regulatory element binding protein 2. Biochem Biophys Res Commun. 2010;393:314-8 pubmed publisher..Here we provide evidence that O-GlcNAc interrupts a known interaction between Sp1 and sterol regulatory element binding protein 2 (SREBP2), thereby inhibiting expression of the gene encoding acetyl-CoA synthetase 1, which is ..
- Yen C, Jiang Y, Shen T, Wong I, Chen C, Chen K, et al. Cloning and expression of the genes associated with lipid metabolism in Tsaiya ducks. Poult Sci. 2005;84:67-74 pubmed publisher..Therefore, laying may affect particular aspects of lipid metabolism, especially biochemical pathways that involved apoVLDL-II and HMG-CoA reductase...
- Jeong H, Lee H, Kim K, Kim Y, Yoon D, Park S. Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2. J Lipid Res. 2008;49:399-409 pubmed..However, in vivo, it is suggested that the sterol-dependent regulation of PCSK9 is mediated predominantly by SREBP-2. ..
- Miserez A, Muller P, Barella L, Barella S, Staehelin H, Leitersdorf E, et al. Sterol-regulatory element-binding protein (SREBP)-2 contributes to polygenic hypercholesterolaemia. Atherosclerosis. 2002;164:15-26 pubmed
- Xiao H, Lu M, Lin T, Chen Z, Chen G, Wang W, et al. Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility. Circulation. 2013;128:632-42 pubmed publisher..immune response to form the NLRP3 inflammasome scaffold in vascular endothelial cells via sterol regulatory element binding protein 2 (SREBP2). Oscillatory flow activates SREBP2 and induces NLRP3 inflammasome in endothelial cells...
- Horton J, Shah N, Warrington J, Anderson N, Park S, Brown M, et al. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci U S A. 2003;100:12027-32 pubmed
- Park C, Jun H, Wakita T, Cheong J, Hwang S. Hepatitis C virus nonstructural 4B protein modulates sterol regulatory element-binding protein signaling via the AKT pathway. J Biol Chem. 2009;284:9237-46 pubmed publisher..These results strongly suggest that NS4B may play an important role in HCV-associated liver pathogenesis by modulating the SREBP signaling pathway. ..
- Soccio R, Adams R, Maxwell K, Breslow J. Differential gene regulation of StarD4 and StarD5 cholesterol transfer proteins. Activation of StarD4 by sterol regulatory element-binding protein-2 and StarD5 by endoplasmic reticulum stress. J Biol Chem. 2005;280:19410-8 pubmed..Because StarD4 is regulated by sterols via SREBP-2, whereas StarD5 is activated by ER stress, they likely serve distinct functions in cholesterol metabolism. ..
- Torre Villalvazo I, Tovar A, Ramos BarragÃ¡n V, CerbÃ³n Cervantes M, Torres N. Soy protein ameliorates metabolic abnormalities in liver and adipose tissue of rats fed a high fat diet. J Nutr. 2008;138:462-8 pubmed..These results suggest that the type of protein consumed and the presence of fat in the diet modulate lipid metabolism in adipose tissue and liver. ..
- 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. ..
- 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...
- Du X, Kristiana I, Wong J, Brown A. Involvement of Akt in ER-to-Golgi transport of SCAP/SREBP: a link between a key cell proliferative pathway and membrane synthesis. Mol Biol Cell. 2006;17:2735-45 pubmed..Our results provide a crucial mechanistic link between the SREBP and PI3K/Akt pathways that may be reconciled teleologically because synthesis of new membrane is an absolute requirement for cell growth and proliferation. ..
- 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. ..
- 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
- Kammoun H, Chabanon H, Hainault I, Luquet S, Magnan C, Koike T, et al. GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice. J Clin Invest. 2009;119:1201-15 pubmed publisher..These findings demonstrate that GRP78 inhibits both insulin-dependent and ER stress-dependent SREBP-1c proteolytic cleavage and explain the role of ER stress in hepatic steatosis in obese rodents. ..
- Caballero F, Fernandez A, De Lacy A, Fernandez Checa J, Caballeria J, Garcia Ruiz C. Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH. J Hepatol. 2009;50:789-96 pubmed publisher..Due to the emerging role of free cholesterol (FC) in NAFLD, our aim was to examine the correlation between FC accumulation in patients with NAFLD and the expression of enzymes that regulate cholesterol homeostasis...
- Krycer J, Brown A. Cross-talk between the androgen receptor and the liver X receptor: implications for cholesterol homeostasis. J Biol Chem. 2011;286:20637-47 pubmed publisher..Given the cross-talk between other steroid hormone receptors and LXR, hormonal regulation of cholesterol via LXR may occur in a variety of cellular contexts. ..
- Garige M, Gong M, Varatharajalu R, Lakshman M. Quercetin up-regulates paraoxonase 1 gene expression via sterol regulatory element binding protein 2 that translocates from the endoplasmic reticulum to the nucleus where it specifically interacts with sterol responsive element-like sequence in parao. Metabolism. 2010;59:1372-8 pubmed publisher..the effects of quercetin on PON1 gene expression, activity, protein level, nuclear mature sterol regulatory element binding protein 2 (SREBP2) level, and its translocation from the endoplasmic reticulum to nucleus and its ..
- Maxwell K, Soccio R, Duncan E, Sehayek E, Breslow J. Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. J Lipid Res. 2003;44:2109-19 pubmed
- 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...
- 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
- Colgan S, Tang D, Werstuck G, Austin R. Endoplasmic reticulum stress causes the activation of sterol regulatory element binding protein-2. Int J Biochem Cell Biol. 2007;39:1843-51 pubmed..These results imply that ER stress-induced SREBP-2 activation occurs through the conventional pathway that normally regulates SREBP in accordance with intracellular sterol concentration. ..
- Li Y, Xu S, Mihaylova M, Zheng B, Hou X, Jiang B, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 2011;13:376-388 pubmed publisher..AMPK-dependent phosphorylation of SREBP may offer therapeutic strategies to combat insulin resistance, dyslipidemia, and atherosclerosis. ..
- Zhao L, Chen Y, Tang R, Chen Y, Li Q, Gong J, et al. Inflammatory stress exacerbates hepatic cholesterol accumulation via increasing cholesterol uptake and de novo synthesis. J Gastroenterol Hepatol. 2011;26:875-83 pubmed publisher..demonstrated that inflammatory stress increased hepatic cholesterol accumulation and enhanced sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLr) and HMGCoA-r mRNA and protein expression in ..
- Rayner K, Suarez Y, Davalos A, Parathath S, Fitzgerald M, Tamehiro N, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328:1570-3 pubmed publisher..Conversely, silencing of miR-33 in vivo increases hepatic expression of ABCA1 and plasma HDL levels. Thus, miR-33 appears to regulate both HDL biogenesis in the liver and cellular cholesterol efflux...