INSIG1

Summary

Gene Symbol: INSIG1
Description: insulin induced gene 1
Alias: CL6, insulin-induced gene 1 protein, INSIG-1 membrane protein
Species: human
Products:     INSIG1

Top Publications

  1. 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
    ..whether the common variants of genes from the SREBP2 activating-related pathway, involving SREBP2, SCAP, INSIG1 and INSIG2 genes, were associated with coronary heart disease (CHD) of Chinese Han population individually or ..
  2. Lee J, Song B, DeBose Boyd R, Ye J. Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78. J Biol Chem. 2006;281:39308-15 pubmed
  3. Li J, Takaishi K, Cook W, McCorkle S, Unger R. Insig-1 "brakes" lipogenesis in adipocytes and inhibits differentiation of preadipocytes. Proc Natl Acad Sci U S A. 2003;100:9476-81 pubmed
    ..The results suggest that insig-1 expression restricts lipogenesis in mature adipocytes and blocks differentiation in preadipocytes. ..
  4. Feramisco J, Goldstein J, Brown M. Membrane topology of human insig-1, a protein regulator of lipid synthesis. J Biol Chem. 2004;279:8487-96 pubmed
    ..The membranous nature of Insig-1 is consistent with its sterol-dependent binding to hydrophobic sterol-sensing domains in SCAP and HMG CoA reductase. ..
  5. Song B, Sever N, DeBose Boyd R. Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. Mol Cell. 2005;19:829-40 pubmed
    ..The current results identify gp78 as the E3 that initiates sterol-accelerated degradation of reductase, and Insig-1 as a bridge between gp78/VCP and the reductase substrate. ..
  6. Sever N, Yang T, Brown M, Goldstein J, DeBose Boyd R. Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain. Mol Cell. 2003;11:25-33 pubmed
    ..Insig-1 appears to play an essential role in the sterol-mediated trafficking of two proteins with sterol-sensing domains, HMG CoA reductase and SCAP. ..
  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. Liou Y, Bai Y, Lin E, Chen J, Chen T, Hong C, et al. Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics. Pharmacogenomics J. 2012;12:54-61 pubmed publisher
    ..In this genetic case-control study, we investigated whether the common variants in INSIG1 and INSIG2 genes were associated with MetS in schizophrenic patients treated with atypical antipsychctics...
  9. Jo Y, Lee P, Sguigna P, DeBose Boyd R. Sterol-induced degradation of HMG CoA reductase depends on interplay of two Insigs and two ubiquitin ligases, gp78 and Trc8. Proc Natl Acad Sci U S A. 2011;108:20503-8 pubmed publisher
    ..Variations in the concentrations of any one of these proteins may account for differences in cell- and/or tissue-specific regulation of reductase degradation. ..

More Information

Publications99

  1. 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. ..
  2. 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. ..
  3. Lee J, Ye J. Proteolytic activation of sterol regulatory element-binding protein induced by cellular stress through depletion of Insig-1. J Biol Chem. 2004;279:45257-65 pubmed
    ..The current study demonstrates that animal cells, in response to either hypotonic shock or ER stress, can bypass the cholesterol inhibition of SREBP processing, an effect that is attributable to the rapid turnover of Insig-1. ..
  4. Lee J, Zhang X, Feramisco J, Gong Y, Ye J. Unsaturated fatty acids inhibit proteasomal degradation of Insig-1 at a postubiquitination step. J Biol Chem. 2008;283:33772-83 pubmed publisher
    ..The current study provides a molecular mechanism for regulation of proteasome-mediated ER protein degradation at a postubiquitination step. ..
  5. 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
    ..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 gain...
  6. Stefan J, Kus K, Wisniewska A, Lorkowska Zawicka B, Kaminski K, Szczubialka K, et al. The antiatherogenic effect of new biocompatible cationically modified polysaccharides: chitosan and pullulan - the comparison study. J Physiol Pharmacol. 2018;69: pubmed publisher
    ..On the other hand, Pull-GTMAC caused a statistically significant increase in insulin induced gene 1 (INSIG1) expression and increase in mRNA level of LDL receptor in brown fat tissue of female apoE-knockout mice after oral ..
  7. Lopreiato V, Hosseini A, Rosa F, Zhou Z, Alharthi A, Trevisi E, et al. Dietary energy level affects adipose depot mass but does not impair in vitro subcutaneous adipose tissue response to short-term insulin and tumor necrosis factor-α challenge in nonlactating, nonpregnant Holstein cows. J Dairy Sci. 2018;101:10206-10219 pubmed publisher
    ..of in vitro treatment, feeding OVE upregulated PPARG, fatty acid synthase (FASN), and insulin induced gene 1 (INSIG1). Abundance of PPARG was greater in SAT of OVE cows cultured individually with INS and TNF...
  8. Li C, Wang M, Zhang T, He Q, Shi H, Luo J, et al. Insulin-induced gene 1 and 2 isoforms synergistically regulate triacylglycerol accumulation, lipid droplet formation, and lipogenic gene expression in goat mammary epithelial cells. J Dairy Sci. 2019;102:1736-1746 pubmed publisher
    The insulin-induced genes INSIG1 and INSIG2 (INSIG) are known to regulate adipogenesis in nonruminants...
  9. Chen C, Wang S, Zhang M, Chen B, You C, Xie D, et al. miR-24 is involved in vertebrate LC-PUFA biosynthesis as demonstrated in marine teleost Siganus canaliculatus. Biochim Biophys Acta Mol Cell Biol Lipids. 2019;1864:619-628 pubmed publisher
    ..While opposite results were observed on the expression of insulin-induced gene 1 (insig1), an endoplasmic reticulum membrane protein blocking Srebp1 proteolytic activation...
  10. Yamanishi K, Maeda S, Kuwahara Otani S, Hashimoto T, Ikubo K, Mukai K, et al. Deficiency in interleukin-18 promotes differentiation of brown adipose tissue resulting in fat accumulation despite dyslipidemia. J Transl Med. 2018;16:314 pubmed publisher
    ..the 'Quantity of adipocytes' identified three associated genes, apolipoprotein C3 (Apoc3), insulin-induced gene 1 (Insig1) and vitamin D (1,25-dihydroxyvitamin D3) receptor (Vdr)...
  11. Do D, Schenkel F, Miglior F, Zhao X, Ibeagha Awemu E. Genome wide association study identifies novel potential candidate genes for bovine milk cholesterol content. Sci Rep. 2018;8:13239 pubmed publisher
    ..9?Mb on chromosome (BTA) 17 and 1.6-3.2?Mb on BTA 14, respectively. DGAT1, PTPN1, INSIG1, HEXIM1, SDS, and HTR5A genes, also known to be associated with human plasma CHL phenotypes, were identified as ..
  12. Nakao R, Yamamoto S, Horikawa K, Yasumoto Y, Nikawa T, Mukai C, et al. Atypical expression of circadian clock genes in denervated mouse skeletal muscle. Chronobiol Int. 2015;32:486-96 pubmed publisher
    ..denervation-sensitive genes included the lipid metabolism-related genes, Nrip1, Bbs1, Ptgis, Acot1, Scd2, Hpgd, Insig1, Dhcr24, Ldlr and Mboat1...
  13. Malmgren S, Spégel P, Danielsson A, Nagorny C, Andersson L, Nitert M, et al. Coordinate changes in histone modifications, mRNA levels, and metabolite profiles in clonal INS-1 832/13 β-cells accompany functional adaptations to lipotoxicity. J Biol Chem. 2013;288:11973-87 pubmed publisher
    ..Thus, Insig1, Lss, Peci, Idi1, Hmgcs1, and Casr were subject to epigenetic regulation...
  14. Liu L, Wang Q, Wang Q, Zhao X, Zhao P, Geng T, et al. Role of miR29c in goose fatty liver is mediated by its target genes that are involved in energy homeostasis and cell growth. BMC Vet Res. 2018;14:325 pubmed publisher
    ..To address the function of miR29c, three predicted target genes (i.e., Insig1, Sgk1 and Col3a1) that participate in energy homeostasis or cell growth were validated by a dual-fluorescence ..
  15. Chu M, Zhao Y, Feng Y, Zhang H, Liu J, Cheng M, et al. MicroRNA-126 participates in lipid metabolism in mammary epithelial cells. Mol Cell Endocrinol. 2017;454:77-86 pubmed publisher
    ..lipid synthesis in MECs in part through increasing levels of the lipid synthesis enzymes FASN, ACSL1, and Insig1. Overexpression of miR-126-3p decreased lipid content in MECs with a reduction in FASN and Insig1...
  16. Carreno D, Hervás G, Toral P, Castro Carrera T, Frutos P. Fish oil-induced milk fat depression and associated downregulation of mammary lipogenic genes in dairy ewes. J Dairy Sci. 2016;99:7971-7981 pubmed publisher
    ..Among the other studied transcription factors, the tendency to a downregulation of INSIG1 was associated with that of SREBF1, whereas no variation was detected for SCAP or THRSP...
  17. Fougère H, Bernard L. Effect of diets supplemented with starch and corn oil, marine algae, or hydrogenated palm oil on mammary lipogenic gene expression in cows and goats: A comparative study. J Dairy Sci. 2019;102:768-779 pubmed publisher
    ..in the mammary expression of 21 genes involved in major lipid pathways, except for 3 transcription factors: PPARA, INSIG1, and SP1...
  18. Helmering J, Juan T, Li C, Chhoa M, Baron W, Gyuris T, et al. A mutation in Ampd2 is associated with nephrotic syndrome and hypercholesterolemia in mice. Lipids Health Dis. 2014;13:167 pubmed publisher
    ..and hypercholesterolemia, we analyzed hepatic gene expression and found the downregulation of Ldlr, Hmgcs and Insig1 and upregulation of Cyp7A1 genes...
  19. Schultz D, Krishna A, Vittitow S, Alizadeh Rad N, Muluhngwi P, Rouchka E, et al. Transcriptomic response of breast cancer cells to anacardic acid. Sci Rep. 2018;8:8063 pubmed publisher
    ..Only six genes were commonly altered by AnAc in both cell lines: SCD, INSIG1, and TGM2 were decreased and PDK4, GPR176, and ZBT20 were increased...
  20. Orekhov A, Pushkarsky T, Oishi Y, Nikiforov N, Zhelankin A, Dubrovsky L, et al. HDL activates expression of genes stimulating cholesterol efflux in human monocyte-derived macrophages. Exp Mol Pathol. 2018;105:202-207 pubmed publisher
    ..monocyte-derived macrophages and identified three genes, fatty acid desaturase 1 (FADS1), insulin induced gene 1 (INSIG1), and the low-density lipoprotein receptor (LDLR), expression of which was significantly upregulated by HDL...
  21. Yu Y, Pierciey F, Maguire T, Alwine J. PKR-like endoplasmic reticulum kinase is necessary for lipogenic activation during HCMV infection. PLoS Pathog. 2013;9:e1003266 pubmed publisher
    ..also suggest that the induction of PERK in HCMV-infected cells stimulates SREBP1 cleavage by reducing levels of Insig1 (Insulin inducible gene 1) protein; this occurs independent of the phosphorylation of eIF2?...
  22. Wang S, Feng L, Meng Z. Bicluster and pathway enrichment analysis related to tumor progression of hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 2015;19:1191-7 pubmed
    ..might play crucial roles in the progression of hepatocellular carcinoma, such as GADD45G, SPTBN1, CDC27, TPD52 and INSIG1. GADD45G and SPTBN1 not only contribute to tumor progression in hepatocellular carcinoma, but also correlate with ..
  23. Tsushima H, Tang Y, Puviindran V, Hsu S, Nadesan P, Yu C, et al. Intracellular biosynthesis of lipids and cholesterol by Scap and Insig in mesenchymal cells regulates long bone growth and chondrocyte homeostasis. Development. 2018;145: pubmed publisher
    ..Here, we have investigated conditional deletion of Scap or of Insig1 and Insig2 (Scap inhibits intracellular biosynthesis and Insig proteins activate intracellular ..
  24. Fűri I, Kalmár A, Wichmann B, Spisák S, Schöller A, Barták B, et al. Cell Free DNA of Tumor Origin Induces a 'Metastatic' Expression Profile in HT-29 Cancer Cell Line. PLoS ONE. 2015;10:e0131699 pubmed publisher
    ..e. TACSTD2, MACC1, MALAT1), tumor biomarker (CEACAM5), metabolic genes (i.e. INSIG1, LIPG), messenger molecule genes (i.e. DAPP, CREB3L2)...
  25. Ali S, Al Jazrawe M, Ma H, Whetstone H, Poon R, Farr S, et al. Regulation of Cholesterol Homeostasis by Hedgehog Signaling in Osteoarthritic Cartilage. Arthritis Rheumatol. 2016;68:127-37 pubmed publisher
    ..To investigate the effects of chondrocyte-specific sterol accumulation, we generated mice lacking Insig1 and Insig2, which are major negative regulators of cholesterol homeostasis, under Col2a1 regulatory elements...
  26. Kalantarian S, Rimm E, Herrington D, Mozaffarian D. Dietary macronutrients, genetic variation, and progression of coronary atherosclerosis among women. Am Heart J. 2014;167:627-635.e1 pubmed publisher
    ..acid and carbohydrate metabolism: sterol regulatory element binding protein-1 (SREBP1), insulin-induced gene-1 (INSIG1), and SREBP cleavage-activating protein (SCAP). Diet was assessed at baseline...
  27. Wang Q, Liu X, Cui Y, Tang Y, Chen W, Li S, et al. The E3 ubiquitin ligase AMFR and INSIG1 bridge the activation of TBK1 kinase by modifying the adaptor STING. Immunity. 2014;41:919-33 pubmed publisher
    ..endoplasmic reticulum (ER) protein AMFR was recruited to and interacted with STING in an insulin-induced gene 1 (INSIG1)-dependent manner...
  28. Tsai Y, Chen H, Chen S, Cheng W, Wang H, Shen Z, et al. TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator. Genome Biol. 2014;15:513 pubmed publisher
    ..We characterize one of the genes, INSIG1 (insulin induced gene 1), to confirm its expression and the 5hmC levels in its promoter...
  29. Wang H, Luo J, Zhang T, Tian H, Ma Y, Xu H, et al. MicroRNA-26a/b and their host genes synergistically regulate triacylglycerol synthesis by targeting the INSIG1 gene. RNA Biol. 2016;13:500-10 pubmed publisher
    ..Insulin-induced gene 1 (INSIG1) encodes a protein with a key role in the regulation of lipogenesis in rodent liver...
  30. Liu F, Song J, Shang X, Meng X, Ma J, Wang H. The gene-gene interaction of INSIG-SCAP-SREBP pathway on the risk of obesity in Chinese children. Biomed Res Int. 2014;2014:538564 pubmed publisher
    ..nucleotide polymorphisms (SNPs) of five genes in INSIG-SCAP-SREBP pathway, including insulin induced gene 1 (INSIG1), insulin induced gene 2 (INSIG2), SREBP cleavage-activating protein gene (SCAP), sterol regulatory element ..
  31. Wang H, Luo J, He Q, Yao D, Wu J, Loor J. miR-26b promoter analysis reveals regulatory mechanisms by lipid-related transcription factors in goat mammary epithelial cells. J Dairy Sci. 2017;100:5837-5849 pubmed publisher
    ..its host gene CTDSP1 regulate triacylglycerol synthesis by synergistically suppressing the insulin-induced gene 1 (INSIG1); however, the direct regulators of miR-26b expression remain unknown...
  32. Gölz L, Buerfent B, Hofmann A, Rühl H, Fricker N, Stamminger W, et al. Genome-wide transcriptome induced by nickel in human monocytes. Acta Biomater. 2016;43:369-382 pubmed publisher
    ..PTGS2?, MTs?, SLCs?), we identified new candidates implicated in Ni(2+)-elicited processes (various microRNAs?, INSIG1?, NAMPT?, MS4A6A?, DHRS9?)...
  33. Zambrano T, Hirata R, Hirata M, Cerda A, Salazar L. Statins differentially modulate microRNAs expression in peripheral cells of hyperlipidemic subjects: A pilot study. Eur J Pharm Sci. 2018;117:55-61 pubmed publisher
    ..Network analysis indicated that atorvastatin-modulated miRNAs regulate key cholesterol genes (ABCA1, HMGCR, INSIG1, LDLR, LPL, SCAP and SREBF1)...
  34. Chen H, Wu K. Epigenetics, TET proteins, and hypoxia in epithelial-mesenchymal transition and tumorigenesis. Biomedicine (Taipei). 2016;6:1 pubmed publisher
    ..regulates glucose metabolism and hypoxia-induced EMT through enhancing the expression of insulin induced gene 1 (INSIG1)...
  35. Wang H, Shi H, Luo J, Yi Y, Yao D, Zhang X, et al. MiR-145 Regulates Lipogenesis in Goat Mammary Cells Via Targeting INSIG1 and Epigenetic Regulation of Lipid-Related Genes. J Cell Physiol. 2017;232:1030-1040 pubmed publisher
    ..Luciferase reporter assays confirmed that insulin induced gene 1 (INSIG1) is a direct target of miR-145...
  36. Xu H, Luo J, Zhao W, Yang Y, Tian H, Shi H, et al. Overexpression of SREBP1 (sterol regulatory element binding protein 1) promotes de novo fatty acid synthesis and triacylglycerol accumulation in goat mammary epithelial cells. J Dairy Sci. 2016;99:783-95 pubmed publisher
    ..We observed a >10-fold increase in expression of INSIG1 but SCAP was downregulated by Ad-nSREBP1...
  37. Balakumar M, Raji L, Prabhu D, Sathishkumar C, Prabu P, Mohan V, et al. High-fructose diet is as detrimental as high-fat diet in the induction of insulin resistance and diabetes mediated by hepatic/pancreatic endoplasmic reticulum (ER) stress. Mol Cell Biochem. 2016;423:93-104 pubmed
    ..Transcription factors of ?-cell function (INSIG1, SREBP1c and PDX1) as well as hepatic gluconeogenesis (FOXO1 and PEPCK) were adversely affected in diet-induced ..
  38. Deng T, Pang C, Ma X, Lu X, Duan A, Zhu P, et al. Four novel polymorphisms of buffalo INSIG2 gene are associated with milk production traits in Chinese buffaloes. Mol Cell Probes. 2016;30:294-299 pubmed publisher
    Insulin-induced genes (INSIGs), including INSIG1 and INSIG2, are important mediators that play a pivotal role in the lipid metabolism and could cause the retention of the SCAP/SREBP complex...
  39. Toral P, Hervás G, Suarez Vega A, Arranz J, Frutos P. Isolation of RNA from milk somatic cells as an alternative to biopsies of mammary tissue for nutrigenomic studies in dairy ewes. J Dairy Sci. 2016;99:8461-8471 pubmed publisher
    ..of fatty acids to glycerol (LPIN1), as well as of a transcription factor that may regulate their expression (INSIG1). Stable mRNA levels were showed in other candidate genes, such as FABP3, GPAT4, or SCD...
  40. Bottje W, Kong B, Reverter A, Waardenberg A, Lassiter K, Hudson N. Progesterone signalling in broiler skeletal muscle is associated with divergent feed efficiency. BMC Syst Biol. 2017;11:29 pubmed publisher
    ..CA3 and CA4), mitochondrial proteins (CKMT1A), oxidative status (SEPP1, HIG2A) and cholesterol homeostasis (APOA1, INSIG1)...
  41. He P, Sun L, Zhu D, Zhang H, Zhang L, Guo Y, et al. Knock-Down of Endogenous Bornavirus-Like Nucleoprotein 1 Inhibits Cell Growth and Induces Apoptosis in Human Oligodendroglia Cells. Int J Mol Sci. 2016;17:435 pubmed publisher
    ..The top 10 most upregulated genes were PI3, RND3, BLZF1, SOD2, EPGN, SBSN, INSIG1, OSMR, CREB3L2, and MSMO1, and the top 10 most-downregulated genes were KRTAP2-4, FLRT2, DIDO1, FAT4, ESCO2, ..
  42. Kim C, Lee H, Kang H, Shin J, Tak H, Kim W, et al. RNA-binding protein HuD reduces triglyceride production in pancreatic β cells by enhancing the expression of insulin-induced gene 1. Biochim Biophys Acta. 2016;1859:675-85 pubmed publisher
    ..Moreover, downregulation of HuD resulted in a decrease in insulin-induced gene 1 (INSIG1) levels but not in the levels of sterol regulatory element-binding protein 1c (SREBP1c), a key transcription ..
  43. Kondo A, Osawa T. Establishment of an Extracellular Acidic pH Culture System. J Vis Exp. 2017;: pubmed publisher
    ..Three distinct acidic media conditions in this study highly upregulated pH-responsive genes such as MSMO1, INSIG1, and IDI1 compared to hypoxia or nutrient starvation...
  44. Olsvik P, Skjærven K, Søfteland L. Metabolic signatures of bisphenol A and genistein in Atlantic salmon liver cells. Chemosphere. 2017;189:730-743 pubmed publisher
    ..proposes metabolites associated with glucose and glutamate metabolism, glucuronidation detoxification, as well as cyp1a1, vtg1, esr1, ar, dnmt3aa, cdkn1b and insig1 as transcriptional markers for BPA and GEN exposure in fish liver cells.
  45. Miao H, Jiang W, Ge L, Li B, Song B. Tetra-glutamic acid residues adjacent to Lys248 in HMG-CoA reductase are critical for the ubiquitination mediated by gp78 and UBE2G2. Acta Biochim Biophys Sin (Shanghai). 2010;42:303-10 pubmed
    ..In summary, these results identify the tetraglutamic acid residues as a critical motif in HMGCR for the ubiquitination reaction mediated by gp78 and UBE2G2. ..
  46. Xu J, Li L, Wang Y, Li Y, Shan M, Sun S, et al. Hepatocyte-specific deletion of BAP31 promotes SREBP1C activation, promotes hepatic lipid accumulation, and worsens IR in mice. J Lipid Res. 2018;59:35-47 pubmed publisher
    ..Immunoprecipitation assay showed that BAP31 interacts with SREBP1C and insulin-induced gene 1 (INSIG1), and BAP31-deletion reduces INSIG1 expression, suggesting that BAP31 may regulate SREBP1C activity by modulating ..
  47. Smith E, Zhang Y, Baye T, Gawrieh S, Cole R, Blangero J, et al. INSIG1 influences obesity-related hypertriglyceridemia in humans. J Lipid Res. 2010;51:701-8 pubmed publisher
    ..7] on human chromosome 7q36, we examined 29 single nucleotide polymorphisms (SNPs) across INSIG1, a biological candidate gene in the region...
  48. Krapivner S, Chernogubova E, Ericsson M, Ahlbeck Glader C, Hamsten A, van t Hooft F. Human evidence for the involvement of insulin-induced gene 1 in the regulation of plasma glucose concentration. Diabetologia. 2007;50:94-102 pubmed
    Insulin-induced gene 1 (INSIG1) is a protein that blocks proteolytic activation of sterol regulatory element-binding proteins (SREBPs), transcription factors that activate genes regulating cholesterol and fatty acid metabolism and ..
  49. Lee J, Gong Y, Zhang X, Ye J. Proteasomal degradation of ubiquitinated Insig proteins is determined by serine residues flanking ubiquitinated lysines. Proc Natl Acad Sci U S A. 2006;103:4958-63 pubmed
    ..The current studies indicate that the degradation of ubiquitinated Insigs is controlled by serine residues flanking the sites of ubiquitination. ..
  50. Sun L, Li L, Goldstein J, Brown M. Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro. J Biol Chem. 2005;280:26483-90 pubmed publisher
    ..This hexapeptide acts as a sterol-regulated ER sorting signal. These studies define the biochemical parameters responsible for regulated sorting of an ER membrane protein into COPII-coated vesicles...
  51. Engelking L, Kuriyama H, Hammer R, Horton J, Brown M, Goldstein J, et al. Overexpression of Insig-1 in the livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis. J Clin Invest. 2004;113:1168-75 pubmed
    ..These results provide in vivo support for the hypothesis that nSREBPs are essential for high levels of lipid synthesis in the liver and indicate that Insig's modulate nSREBP levels by binding and retaining SCAP in the ER. ..
  52. Janowski B. The hypocholesterolemic agent LY295427 up-regulates INSIG-1, identifying the INSIG-1 protein as a mediator of cholesterol homeostasis through SREBP. Proc Natl Acad Sci U S A. 2002;99:12675-80 pubmed
    ..Taken together, these data suggest that INSIG-1 plays a critical role in regulating cholesterol concentrations in the cell. ..
  53. Zhang Y, Motamed M, Seemann J, Brown M, Goldstein J. Point mutation in luminal loop 7 of Scap protein blocks interaction with loop 1 and abolishes movement to Golgi. J Biol Chem. 2013;288:14059-67 pubmed publisher
    ..These data suggest that Scap Loop 1 must interact with Loop 7 to maintain Loop 6 in the configuration that permits COPII binding. These results help explain the operation of Scap as a sterol sensor. ..
  54. Szczesna Skorupa E, Kemper B. Progesterone receptor membrane component 1 inhibits the activity of drug-metabolizing cytochromes P450 and binds to cytochrome P450 reductase. Mol Pharmacol. 2011;79:340-50 pubmed publisher
    ..Furthermore, PGRMC1 binds to CPR, which may influence P450 activity. ..
  55. Bai R, Latifi Z, Kusama K, Nakamura K, Shimada M, Imakawa K. Induction of immune-related gene expression by seminal exosomes in the porcine endometrium. Biochem Biophys Res Commun. 2018;495:1094-1101 pubmed publisher
    ..The decrease in PMVK, SC5D, INSIG1, HSD17B7, NSDHL, HMGCR, SQLE and FDFT1, and increase in CCL20, TNFSF15, AMCFII, CXCL2 and CXCL8 were also found in ..
  56. Lou H, Le F, Zheng Y, Li L, Wang L, Wang N, et al. Assisted reproductive technologies impair the expression and methylation of insulin-induced gene 1 and sterol regulatory element-binding factor 1 in the fetus and placenta. Fertil Steril. 2014;101:974-980.e2 pubmed publisher
    ..Meanwhile, in ICSI-conceived fetuses, the expression of INSIG1 was significantly higher, and methylation rates were lower, than in the IVF and control groups...
  57. Wang G, Zhang X, Lee J, Wang X, Yang Z, Zhang K. Endoplasmic reticulum factor ERLIN2 regulates cytosolic lipid content in cancer cells. Biochem J. 2012;446:415-25 pubmed publisher
    ..ERLIN2 was found to bind to INSIG1 (insulin-induced gene 1), a key ER membrane protein that blocks SREBP activation...
  58. Lee P, DeBose Boyd R. Intramembrane glycine mediates multimerization of Insig-2, a requirement for sterol regulation in Chinese hamster ovary cells. J Lipid Res. 2010;51:192-201 pubmed publisher
    ..These studies identify the intramembrane glycine as a key residue for normal sterol regulation in animal cells. ..
  59. Leichner G, Avner R, Harats D, Roitelman J. Dislocation of HMG-CoA reductase and Insig-1, two polytopic endoplasmic reticulum proteins, en route to proteasomal degradation. Mol Biol Cell. 2009;20:3330-41 pubmed publisher
  60. Sever N, Lee P, Song B, Rawson R, DeBose Boyd R. Isolation of mutant cells lacking Insig-1 through selection with SR-12813, an agent that stimulates degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem. 2004;279:43136-47 pubmed
    ..These results provide formal genetic proof for the essential role of Insig-1 in feedback control of lipid synthesis in cultured cells. ..
  61. Adams C, Goldstein J, Brown M. Cholesterol-induced conformational change in SCAP enhanced by Insig proteins and mimicked by cationic amphiphiles. Proc Natl Acad Sci U S A. 2003;100:10647-52 pubmed
    ..The effects of cationic amphiphiles raise the possibility that SCAP may monitor specifically the composition of the cytoplasmic leaflet of the ER membrane. ..
  62. Yabe D, Xia Z, Adams C, Rawson R. Three mutations in sterol-sensing domain of SCAP block interaction with insig and render SREBP cleavage insensitive to sterols. Proc Natl Acad Sci U S A. 2002;99:16672-7 pubmed publisher
    ..Thus, three different point mutations, each within the sterol-sensing domain of SCAP, prevent sterol-induced binding of SCAP to insig proteins and abolish feedback regulation of SREBP processing by sterols...
  63. Jo Y, Hartman I, DeBose Boyd R. Ancient ubiquitous protein-1 mediates sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl CoA reductase in lipid droplet-associated endoplasmic reticulum membranes. Mol Biol Cell. 2013;24:169-83 pubmed publisher
  64. Huber M, Vesely P, Datta K, Gerace L. Erlins restrict SREBP activation in the ER and regulate cellular cholesterol homeostasis. J Cell Biol. 2013;203:427-36 pubmed publisher
    ..We speculate that erlins promote stability of the SREBP-Scap-Insig complex and may contribute to the highly cooperative control of this system. ..
  65. Rodrigue Way A, Caron V, Bilodeau S, Keil S, Hassan M, Levy E, et al. Scavenger receptor CD36 mediates inhibition of cholesterol synthesis via activation of the PPAR?/PGC-1? pathway and Insig1/2 expression in hepatocytes. FASEB J. 2014;28:1910-23 pubmed publisher
    ..b>Insig1 and Insig2 gene expression was also increased through activation of nuclear receptor peroxisome-proliferator ..
  66. Wang K, Zhang Q, Liu X, Wu L, Zeng M. PKNOX2 is associated with formal thought disorder in schizophrenia: a meta-analysis of two genome-wide association studies. J Mol Neurosci. 2012;48:265-72 pubmed publisher
    ..12?×?10(-5)). In conclusion, we identified four new loci (PKNOX2, MYH13, PHF2, and GPC6) associated with FTD. These findings offer the potential for new insights into the pathogenesis of FTD and schizophrenia. ..
  67. Kaneda A, Kaminishi M, Nakanishi Y, Sugimura T, Ushijima T. Reduced expression of the insulin-induced protein 1 and p41 Arp2/3 complex genes in human gastric cancers. Int J Cancer. 2002;100:57-62 pubmed
    ..RT-PCR analysis of the 4 genes showed reduced expression of 2 genes in cancers: Insulin-induced protein 1 (INSIG1/CL-6) and p41 Arp2/3 complex (p41-Arc)...
  68. Suchanek M, Radzikowska A, Thiele C. Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells. Nat Methods. 2005;2:261-7 pubmed
    ..Applying this technology to membrane protein complexes, we discovered a previously unknown direct interaction of the progesterone-binding membrane protein PGRMC1 with Insig-1, a key regulator of cholesterol homeostasis. ..
  69. Kranc W, Brazert M, Ozegowska K, Nawrocki M, Budna J, Celichowski P, et al. Expression Profile of Genes Regulating Steroid Biosynthesis and Metabolism in Human Ovarian Granulosa Cells-A Primary Culture Approach. Int J Mol Sci. 2017;18: pubmed publisher
    ..Out of those, ten genes, namely STAR, SCAP, POR, SREBF1, GFI1, SEC14L2, STARD4, INSIG1, DHCR7, and IL1B, belong to both groups...
  70. Liu S, Xie F, Xiang X, Liu S, Dong S, Qu K, et al. Identification of differentially expressed genes, lncRNAs and miRNAs which are associated with tumor malignant phenotypes in hepatoblastoma patients. Oncotarget. 2017;8:97554-97564 pubmed publisher
    ..XR_245338, XR_428373, XR_924945, XR_929728, XR_931611, XR_935074 and XR_946696), and 6 mRNAs (EGFR, GAREM, INSIG1, KRT81, SAR1B and SDC1) were selected to conduct a lncRNA-miRNA-mRNA network...
  71. Szopa M, Meirhaeghe A, Luan J, Moreno L, Gonzalez Gross M, Vidal Puig A, et al. No association between polymorphisms in the INSIG1 gene and the risk of type 2 diabetes and related traits. Am J Clin Nutr. 2010;92:252-7 pubmed publisher
    The insulin-induced gene 1 (INSIG1) encodes a protein that blocks proteolytic activation of sterol regulatory element binding proteins, which are transcription factors that activate genes that regulate cholesterol, fatty acid, and glucose ..
  72. Loh W, Yang Y, Lam K. miR-92a enhances recombinant protein productivity in CHO cells by increasing intracellular cholesterol levels. Biotechnol J. 2017;12: pubmed publisher
    ..Here, the authors report the identification of insig1, a regulator of cholesterol biosynthesis, as a target of miR-92a using computational prediction...
  73. Carobbio S, Hagen R, Lelliott C, Slawik M, Medina Gomez G, Tan C, et al. Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity. Diabetes. 2013;62:3697-708 pubmed publisher
    ..Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states...
  74. Dobrosotskaya I, Goldstein J, Brown M, Rawson R. Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs. J Biol Chem. 2003;278:35837-43 pubmed
    ..They indicate that insect cells can respond to sterols when proper regulatory proteins are expressed. ..
  75. Theusch E, Kim K, Stevens K, Smith J, Chen Y, Rotter J, et al. Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner. Pharmacogenomics J. 2017;17:222-229 pubmed publisher
    ..The correlation of insulin-induced gene 1 (INSIG1) expression changes with TG response (rho=0.32, q=0.11) was driven by men (interaction P=0.0055)...
  76. Kim H, Zhang H, Meng D, Russell G, Lee J, Ye J. UAS domain of Ubxd8 and FAF1 polymerizes upon interaction with long-chain unsaturated fatty acids. J Lipid Res. 2013;54:2144-52 pubmed publisher
    ..These results provide further insights into protein-FA interactions by identifying the UAS domain as a motif interacting with long-chain unsaturated FAs. ..
  77. Gong Y, Lee J, Brown M, Goldstein J, Ye J. Juxtamembranous aspartic acid in Insig-1 and Insig-2 is required for cholesterol homeostasis. Proc Natl Acad Sci U S A. 2006;103:6154-9 pubmed
    ..These studies identify a single amino acid residue that is crucial for the function of Insig proteins in regulating cholesterol homeostasis in mammalian cells. ..
  78. Lee J, Brauweiler A, Rudolph M, Hooper J, Drabkin H, Gemmill R. The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways. Mol Cancer Res. 2010;8:93-106 pubmed publisher
    ..Moreover, high-molecular weight ubiquitylated proteins were observed in eIF3 immunoprecipitations from TRC8-overexpressing cells. Thus, TRC8 function may provide a regulatory link between the lipid and protein biosynthetic pathways. ..
  79. Liu X, Li Y, Wang L, Zhao Q, Lu X, Huang J, et al. The INSIG1 gene, not the INSIG2 gene, associated with coronary heart disease: tagSNPs and haplotype-based association study. The Beijing Atherosclerosis Study. Thromb Haemost. 2008;100:886-92 pubmed
    ..The insulin induced gene 1 (INSIG1) and insulin induced gene 2 (INSIG2) encode two proteins which mediate feedback control of cholesterol synthesis...
  80. Ikeda Y, Demartino G, Brown M, Lee J, Goldstein J, Ye J. Regulated endoplasmic reticulum-associated degradation of a polytopic protein: p97 recruits proteasomes to Insig-1 before extraction from membranes. J Biol Chem. 2009;284:34889-900 pubmed publisher
    ..These data suggest that p97 recruits proteasomes to polytopic ER proteins even before they are extracted from membranes. ..
  81. Ganguly B, Ambwani T, Rastogi S. Electronic Northern Analysis of Genes and Modeling of Gene Networks Underlying Bovine Milk Fat Production. Genet Res Int. 2017;2017:1910530 pubmed publisher
    ..13 genes (ACSS1, ACSS2, ADFP, CD36, FABP3, FASN, GPAM, INSIG1, LPL, SCD5, SPTLC1, SREBF1, and XDH) showed higher expression in the ..
  82. Roth A, Looser R, Kaufmann M, Blättler S, Rencurel F, Huang W, et al. Regulatory cross-talk between drug metabolism and lipid homeostasis: constitutive androstane receptor and pregnane X receptor increase Insig-1 expression. Mol Pharmacol. 2008;73:1282-9 pubmed publisher
    ..The fact that drugs that serve as CAR or PXR ligands induce Insig-1 might have clinical consequences and explains alterations lipid levels after drug therapy. ..
  83. Frutos P, Toral P, Hervás G. Individual variation of the extent of milk fat depression in dairy ewes fed fish oil: Milk fatty acid profile and mRNA abundance of candidate genes involved in mammary lipogenesis. J Dairy Sci. 2017;100:9611-9622 pubmed publisher
    ..fish oil showed a tendency to lower the mRNA abundance of lipogenic genes such as ACSS2, FASN, LPIN1, FADS2, and INSIG1, but only SCD and GPAT4 tended to differ between RESPON- and RESPON+...
  84. 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. ..
  85. Schrörs B, Lübcke S, Lennerz V, Fatho M, Bicker A, Wölfel C, et al. HLA class I loss in metachronous metastases prevents continuous T cell recognition of mutated neoantigens in a human melanoma model. Oncotarget. 2017;8:28312-28327 pubmed publisher
    ..These findings corroborate that, although neoantigens represent attractive therapeutic targets, they also contribute to the process of cancer immunoediting as a serious limitation to specific T cell immunotherapy. ..
  86. Figueroa J, Han S, Garcia Closas M, Baris D, Jacobs E, Kogevinas M, et al. Genome-wide interaction study of smoking and bladder cancer risk. Carcinogenesis. 2014;35:1737-44 pubmed publisher
    ..Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer. ..
  87. Cheng C, Ru P, Geng F, Liu J, Yoo J, Wu X, et al. Glucose-Mediated N-glycosylation of SCAP Is Essential for SREBP-1 Activation and Tumor Growth. Cancer Cell. 2015;28:569-581 pubmed publisher
    ..Targeting SCAP N-glycosylation may provide a promising means of treating malignancies and metabolic diseases. ..
  88. Nguyen A, Lee S, DeBose Boyd R. Insig-mediated, sterol-accelerated degradation of the membrane domain of hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase in insect cells. J Biol Chem. 2009;284:26778-88 pubmed publisher
    ..These studies define Insigs as the minimal requirement for sterol-accelerated degradation of the membrane domain of reductase in Drosophila S2 cells. ..
  89. Norman K, Chen T, ZEINER G, Sarnow P. Precursor microRNA-122 inhibits synthesis of Insig1 isoform mRNA by modulating polyadenylation site usage. RNA. 2017;23:1886-1893 pubmed publisher
    The insulin-induced gene 1 protein (Insig1) inhibits the cholesterol biosynthesis pathway by retaining transcription factor SREBP in the endoplasmic reticulum, and by causing the degradation of HMGCR, the rate-limiting enzyme in ..
  90. Peng Y, Schwarz E, Lazar M, Genin A, Spinner N, Taub R. Cloning, human chromosomal assignment, and adipose and hepatic expression of the CL-6/INSIG1 gene. Genomics. 1997;43:278-84 pubmed
    ..CL-6 is now denoted INSIG1 (insulin-induced gene 1)...