The hypocholesterolemic agent LY295427 up-regulates INSIG-1, identifying the INSIG-1 protein as a mediator of cholesterol homeostasis through SREBP
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Oxysterols regulate cholesterol homeostasis through liver X receptor (LXR; cholesterol-lowering)- and sterol regulatory element-binding protein (SREBP; cholesterol-raising)-mediated signaling pathways. Previously we reported that the hypocholesterolemic agent LY295427 (4α-allylcholestan-3α-ol) reverses oxysterol-mediated suppression of SREBP processing. We now report that LY295427 increases expression of insulin-induced gene-1 (INSIG-1) and restores SREBP processing in cells treated with oxysterols. In cells overexpressing the INSIG-1 gene, by contrast, SREBP processing is suppressed and oxysterol regulation is disrupted. SREBP processing is not restored by addition of LY295427, but is restored by increasing the levels of SREBP cleavage-activating protein (SCAP). These findings suggest that the INSIG-1 protein alters sterol balance by modulating SREBP processing jointly with SCAP. To test whether the action of oxysterols on SREBP processing is mediated through endogenous INSIG-1 protein, we used RNAi to lower the expression of the INSIG-1 gene, and found that reduced INSIG-1 protein levels caused the loss of SREBP regulation by oxysterols. We conclude that: ( i ) INSIG-1 gene expression is suppressed by oxysterols; ( ii ) LY295427 treatment counters the suppressive effects of oxysterols on SREBP processing, resulting in the expression of the INSIG-1 gene; and ( iii ) INSIG-1 gene expression affects SREBP processing. Taken together, these data suggest that INSIG-1 plays a critical role in regulating cholesterol concentrations in the cell.
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A previous study showed that LY295427 reverses the effect of 25HC on the SREBP pathway by elevating the expression of Ldlr as well as Insig1, presumably by creating a sink for 25HC.
“A previous study showed that LY295427 reverses the effect of 25HC on the SREBPpathway by elevating the expression of Ldlr (64) as well as Insig1 (44) presumably by creating a sink for 25HC.”
From Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol (2023) · cites this paper as [44]
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Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456 · see citing works
An oxysterol signalling pathway mediated by the nuclear receptor LXRα
Janowski, B. A., Willy, P. J., Devi, T. R., Falck, J. R., & Mangelsdorf, D. J. (1996) · Nature · doi:10.1038/383728a0 · Cited by 1,754 · see citing works
Self-citationRepa, J. J., Liang, G., Ou, J., Bashmakov, Y. K., Lobaccaro, J. A., Shimomura, I., Shan, B., Brown, M. S., Goldstein, J. L., & Mangelsdorf, D. J. (2000) · Genes & Development · doi:10.1101/gad.844900 · Cited by 1,693 · see citing works
[19] Receptor-mediated endocytosis of low-density lipoprotein in cultured cells
Goldstein, J. L., Basu, S. K., & Brown, M. S. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)98152-1 · Cited by 1,623 · see citing works
A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood
Brown, M. S., & Goldstein, J. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11041 · Cited by 1,327 · see citing works
Regulation of Absorption and ABC1-Mediated Efflux of Cholesterol by RXR Heterodimers
Repa, J. J., Turley, S. D., Lobaccaro, J. A., Medina, J. C., Li, L., Lustig, K. D., Shan, B., Heyman, R. A., Dietschy, J. M., & Mangelsdorf, D. J. (2000) · Science · doi:10.1126/science.289.5484.1524 · Cited by 1,303 · see citing works
Activation of the Nuclear Receptor LXR by Oxysterols Defines a New Hormone Response Pathway
Lehmann, J. M., Kliewer, S. A., Moore, L. B., Smith-Oliver, T. A., Oliver, B. B., Su, J.-L., Sundseth, S. S., Winegar, D. A., Blanchard, D. E., Spencer, T. A., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3137 · Cited by 1,233 · see citing works
Crucial Step in Cholesterol Homeostasis
Yang, T., Espenshade, P. J., Wright, M. E., Yabe, D., Gong, Y., Aebersold, R., Goldstein, J. L., & Brown, M. S. (2002) · Cell · doi:10.1016/s0092-8674(02)00872-3 · Cited by 987 · see citing works
Structural requirements of ligands for the oxysterol liver X receptors LXRα and LXRβ
Janowski, B. A., Grogan, M. J., Jones, S. A., Wisely, G. B., Kliewer, S. A., Corey, E. J., & Mangelsdorf, D. J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.1.266 · Cited by 946 · see citing works
Self-citationBrown, M. S., Faust, J. R., Goldstein, J. L., Kaneko, I., & Endo, A. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38120-6 · Cited by 556 · see citing works
Sterol Resistance in CHO Cells Traced to Point Mutation in SREBP Cleavage–Activating Protein
Hua, X., Nohturfft, A., Goldstein, J. L., & Brown, M. S. (1996) · Cell · doi:10.1016/s0092-8674(00)81362-8 · Cited by 474 · see citing works
Rawson, R. B., Zelenski, N. G., Nijhawan, D., Ye, J., Sakai, J., Hasan, M. T., Chang, T., Brown, M. S., & Goldstein, J. L. (1997) · Molecular Cell · doi:10.1016/s1097-2765(00)80006-4 · Cited by 466 · see citing works
Unsaturated Fatty Acids Down-regulate SREBP Isoforms 1a and 1c by Two Mechanisms in HEK-293 Cells
Hannah, V. C., Ou, J., Luong, A., Goldstein, J. L., & Brown, M. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007273200 · Cited by 448 · see citing works
Sakai, J., Rawson, R. B., Espenshade, P. J., Cheng, D., Seegmiller, A. C., Goldstein, J. L., & Brown, M. S. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80150-1 · Cited by 405 · see citing works
Regulated Step in Cholesterol Feedback Localized to Budding of SCAP from ER Membranes
Nohturfft, A., Yabe, D., Goldstein, J. L., Brown, M. S., & Espenshade, P. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00037-4 · Cited by 347 · see citing works
Nohturfft, A., DeBose‐Boyd, R. A., Scheek, S., Goldstein, J. L., & Brown, M. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11235 · Cited by 244 · see citing works
Nohturfft, A., Brown, M. S., & Goldstein, J. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.12848 · Cited by 135 · see citing works
Diamond, R. H., Du, K., Lee, V. M., Mohn, K. L., Haber, B. A., Tewari, D. S., & Taub, R. A. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82454-1 · Cited by 105 · see citing works
Yang, T., Goldstein, J. L., & Brown, M. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005439200 · Cited by 87 · see citing works
SCAP ligands are potent new lipid-lowering drugs
Grand‐Perret, T., Bouillot, A., Perrot, A., Commans, S., Walker, M., & Issandou, M. (2001) · Nature Medicine · doi:10.1038/nm1201-1332 · Cited by 61 · see citing works
Cloning, Human Chromosomal Assignment, and Adipose and Hepatic Expression of the CL-6/INSIG1 Gene
Peng, Y., Schwarz, E. J., Lazar, M. A., Genin, A., Spinner, N. B., & Taub, R. A. (1997) · Genomics · doi:10.1006/geno.1997.4821 · Cited by 60 · see citing works
Janowski, B. A., Shan, B., & Russell, D. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m108348200 · Cited by 59 · see citing works
Self-citationLin, H., Rampersaud, A. A., Archer, R. A., Pawlak, J. M., Beavers, L. S., Schmidt, R. J., Kauffman, R. F., Bensch, W. R., & Bumol, T. F. (1995) · Journal of Medicinal Chemistry · doi:10.1021/jm00002a010 · Cited by 24 · see citing works
Insulin induction ofpip 92, CL-6, and novel mRNAs in rat hepatoma cells
Bortoff, K. D., Zhu, C.-C., Hrywna, Y., & Messina, J. L. (1997) · Endocrine · doi:10.1007/bf02778142 · Cited by 20 · see citing works
Bensch, W. R., Gadski, R. A., Bean, J. S., Beavers, L. S., Schmidt, R. J., Perry, D. N., Murphy, A., McClure, D., Eacho, P. I., Breau, A. P., et al. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38110-8 · Cited by 16 · see citing works
Bowling, N., Matter, W. F., Gadski, R. A., McClure, D. B., Schreyer, T., Dawson, P. A., & Vlahos, C. J. (1996) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37462-9 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- [2]Bensch W R, Gadski R A, Bean J S, Beavers L S, Schmidt R J, Perry D N, Murphy A T, McClure D B, Eacho P I, Breau A P, et al. J Pharmacol Exp Ther. 1999;289:85–289. [PubMed] [Google Scholar]
- [3]Bowling N, Metter W F, Gadski R A, McClure D B, Schreyer T, Dawson P A, Vlahos C J. J Lipid Res. 1996;37:2586–2598. [PubMed] [Google Scholar]
- [10]Diamond R H, Du K, Lee V M, Mohn K L, Haber B A, Tewari D S, Taub R. J Biol Chem. 1993;268:15185–15192. [PubMed] [Google Scholar]
- [14]Brown M S, Faust J R, Goldstein J L. J Biol Chem. 1978;253:1121–1128. [PubMed] [Google Scholar]
- [27]Yang T, Espenshade P J, Wright M E, Yabe D, Gong Y, Aebersold R, Goldstein J L, Brown M S. Cell. 2002;110:489–500. doi: 10.1016/s0092-8674(02)00872-3. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
Cited by
Sorted by citations
Protein Sensors for Membrane Sterols
Goldstein, J. L., DeBose‐Boyd, R. A., & Brown, M. S. (2006) · Cell · doi:10.1016/j.cell.2005.12.022 · Cited by 1,677 · see citing works
Sever, N., Yang, T., Brown, M. S., Goldstein, J. L., & DeBose‐Boyd, R. A. (2003) · Molecular Cell · doi:10.1016/s1097-2765(02)00822-5 · Cited by 376 · see citing works
The SREBP pathway — insights from insigs and insects
Rawson, R. B. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1174 · Cited by 323 · see citing works
SREBPs: the crossroads of physiological and pathological lipid homeostasis
Raghow, R., Yellaturu, C. R., Deng, X., Park, E. A., & Elam, M. B. (2008) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2007.10.009 · Cited by 304 · see citing works
Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks
Yang, X., Deignan, J. L., Qi, H., Zhu, J., Qian, S., Zhong, J., Torosyan, G., Majid, S., Falkard, B., Kleinhanz, R. R., et al. (2009) · Nature Genetics · doi:10.1038/ng.325 · Cited by 288 · see citing works
Liver-specific mRNA for Insig-2 down-regulated by insulin: Implications for fatty acid synthesis
Yabe, D., Komuro, R., Liang, G., Goldstein, J. L., & Brown, M. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0130116100 · Cited by 293 · see citing works
Engelking, L. J., Kuriyama, H., Hammer, R. E., Horton, J. D., Brown, M. S., Goldstein, J. L., & Liang, G. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20978 · Cited by 273 · see citing works
Hepatic gene expression profiles in a long-term high-fat diet-induced obesity mouse model
Kim, S., Sohn, I., Ahn, J., Lee, K.-H., Lee, Y. S., & Lee, Y. S. (2004) · Gene · doi:10.1016/j.gene.2004.06.015 · Cited by 249 · see citing works
Coordination of Lipid Metabolism in Membrane Biogenesis
Nohturfft, A., & Zhang, S. C. (2009) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.24.110707.175344 · Cited by 175 · see citing works
Desiccation Tolerance of Prokaryotes: Application of Principles to Human Cells
Potts, M. (2005) · Integrative and Comparative Biology · doi:10.1093/icb/45.5.800 · Cited by 144 · see citing works
Insulin-induced gene: A new regulator in lipid metabolism
Dong, X., & Tang, S.-Q. (2010) · Peptides · doi:10.1016/j.peptides.2010.07.020 · Cited by 120 · see citing works
Marseille‐Tremblay, C., Éthier‐Chiasson, M., Forest, J., Giguère, Y., Masse, A., Mounier, C., & Lafond, J. (2007) · Molecular Reproduction and Development · doi:10.1002/mrd.20842 · Cited by 111 · see citing works
Kast-Woelbern, H. R., Dana, S. L., Cesario, R. M., Sun, L., de Grandpre, L. Y., Brooks, M. E., Osburn, D. L., Reifel-Miller, A. E., Klausing, K., & Leibowitz, M. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403145200 · Cited by 106 · see citing works
Kim, S., Sohn, I., Sook, L. Y., & Lee, Y. S. (2005) · Journal of Nutrition · doi:10.1093/jn/135.1.33 · Cited by 95 · see citing works
Ribeiro, C. M. P., Hurd, H. L., Wu, Y., Martino, M. E. B., Jones, L. C., Brighton, B. K., Boucher, R. C., & O’Neal, W. K. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005806 · Cited by 93 · see citing works
Matsusue, K., Gavrilova, O., Lambert, G. C., Brewer, H. B., Ward, J. M., Inoue, Y., LeRoith, D., & Gonzalez, F. J. (2004) · Molecular Endocrinology · doi:10.1210/me.2004-0213 · Cited by 80 · see citing works
Macrophage cholesterol transport: a critical player in foam cell formation
Vainio, S., & Ikonen, E. (2003) · Annals of Medicine · doi:10.1080/07853890310008198 · Cited by 80 · see citing works
Webb, L., Sengupta, S., Edell, C., Piedra-Quintero, Z. L., Amici, S. A., Miranda, J. N., Bevins, M. R., Kennemer, A. A., Laliotis, G., Tsichlis, P. N., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci131254 · Cited by 71 · see citing works
Cashikar, A. G., Toral-Rios, D., Timm, D., Romero, J., Strickland, M., Long, J. M., Han, X., Holtzman, D. M., & Paul, S. M. (2023) · Journal of Lipid Research · doi:10.1016/j.jlr.2023.100350 · Cited by 72 · see citing works
Klopotek, A., Hirche, F., & Eder, K. (2006) · Experimental Biology and Medicine · doi:10.1177/153537020623100810 · Cited by 69 · see citing works
Du, X., Pham, Y., & Brown, A. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408690200 · Cited by 69 · see citing works
Taylor, J. M. W., Borthwick, F., Bartholomew, C., & Graham, A. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq015 · Cited by 68 · see citing works
Kovacs, W. J., Tape, K. N., Shackelford, J. E., Wikander, T. M., Richards, M. J., Fliesler, S. J., Krisans, S. K., & Faust, P. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m809064200 · Cited by 66 · see citing works
High-mobility group A1a protein regulates Ras/ERK signaling in MCF-7 human breast cancer cells
Treff, N. R., Pouchnik, D. J., Dement, G. A., Britt, R. L., & Reeves, R. (2004) · Oncogene · doi:10.1038/sj.onc.1207167 · Cited by 63 · see citing works
TNF-α interferes with lipid homeostasis and activates acute and proatherogenic processes
Tacer, K. F., Kuzman, D., Seliškar, M., Pompon, D., & Rozman, D. (2007) · Physiological Genomics · doi:10.1152/physiolgenomics.00264.2006 · Cited by 62 · see citing works
Coulouarn, C., Gómez-Quiroz, L. E., Lee, J., Kaposi-Novák, P., Conner, E. A., Goldina, T. A., Онищенко, Г. Е., Factor, V. M., & Thorgeirsson, S. S. (2006) · Hepatology · doi:10.1002/hep.21293 · Cited by 59 · see citing works
Lee, S., Lee, D.-K., Choi, E., & Lee, J. W. (2004) · Molecular Endocrinology · doi:10.1210/me.2004-0324 · Cited by 58 · see citing works
Characterization of NVX‐207, a novel betulinic acid‐derived anti‐cancer compound
Willmann, M., Wacheck, V., Buckley, J. D., Nagy, K., Thalhammer, J. G., Paschke, R., Triche, T. J., Jansen, B., & Selzer, E. (2009) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2009.02105.x · Cited by 56 · see citing works
Cholesterol: From Feeding to Gene Regulation
Martini, C., & Pallottini, V. (2007) · Genes & Nutrition · doi:10.1007/s12263-007-0049-y · Cited by 53 · see citing works
Regulation of fatty acid and cholesterol synthesis: co-operation or competition?
Gibbons, G. F. (2003) · Progress in Lipid Research · doi:10.1016/s0163-7827(03)00034-1 · Cited by 51 · see citing works
Side-Chain Oxysterols Modulate Cholesterol Accessibility through Membrane Remodeling
Bielska, A. A., Olsen, B. N., Gale, S. E., Mydock-McGrane, L. K., Krishnan, K., Baker, N., Schlesinger, P. H., Covey, D. F., & Ory, D. S. (2014) · Biochemistry · doi:10.1021/bi5000096 · Cited by 49 · see citing works
Sathishkumar, K., Haque, M., Perumal, T. E., Francis, J., & Uppu, R. M. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.10.044 · Cited by 43 · see citing works
Rodrigue‐Way, A., Caron, V., Bilodeau, S., Keil, S., Hassan, M., Levy, E. H., Mitchell, G. A., & Tremblay, A. (2013) · The FASEB Journal · doi:10.1096/fj.13-240168 · Cited by 41 · see citing works
Botolin, D., & Jump, D. Β. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212846200 · Cited by 41 · see citing works
Do, D. N., Schenkel, F. S., Miglior, F., Zhao, X., & Ibeagha-Awemu, E. M. (2018) · Scientific Reports · doi:10.1038/s41598-018-31427-0 · Cited by 38 · see citing works
Cholesterol Homeostasis: Not until the SCAP Lady INSIGs
Loewen, C. J. R., & Levine, T. P. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01292-7 · Cited by 37 · see citing works
Pezacki, J. P., Sagan, S. M., Tonary, A. M., Rouleau, Y., Bélanger, S., Supeková, Ľ., & Su, A. I. (2009) · BMC Chemical Biology · doi:10.1186/1472-6769-9-2 · Cited by 35 · see citing works
Identification of Novel Genes and Pathways Regulating SREBP Transcriptional Activity
Chatterjee, S., Szustakowski, J. D., Nirmala, N., Mickanin, C., Labow, M., Nohturfft, A., Dev, K. K., & Sivasankaran, R. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005197 · Cited by 35 · see citing works
Xu, X., Li, L., Zhang, Y., Lu, X., Lin, W., Wu, S., Qin, X., Xu, R., & Lin, W. (2020) · PLoS ONE · doi:10.1371/journal.pone.0240616 · Cited by 34 · see citing works
25‐Hydroxycholesterol Acts in the Golgi Compartment to Induce Degradation of Tyrosinase
Hall, A. M., Krishnamoorthy, L., & Orlow, S. J. (2004) · Pigment Cell Research · doi:10.1111/j.1600-0749.2004.00161.x · Cited by 27 · see citing works
Fatima, S. S., Khalid, E., Ladak, A. A., & Ali, S. A. (2018) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2018.1454422 · Cited by 25 · see citing works
Membrane cholesterol as regulator of human rhomboid protease RHBDL4
Paschkowsky, S., Recinto, S. J., Young, J. C., Bondar, A., & Munter, L. M. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002640 · Cited by 25 · see citing works
Kim, C., Lee, H., Kang, H., Shin, J. J., Tak, H., Kim, W., Gorospe, M., & Lee, E. K. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.02.017 · Cited by 25 · see citing works
Ali, F., Ismail, A., Esa, N. M., Chong, P. P., & Kersten, S. (2015) · Journal of Functional Foods · doi:10.1016/j.jff.2015.06.047 · Cited by 24 · see citing works
Caloric restrictions affect some factors involved in age‐related hypercholesterolemia
Martini, C., Pallottini, V., Cavallini, G., Donati, A., Bergamini, E., & Trentalance, A. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21158 · Cited by 23 · see citing works
Tacer, K. F., Bognar, S. K., Waterman, M. R., & Rozman, D. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00191-2 · Cited by 22 · see citing works
Keeton, A. B., Bortoff, K. D., Franklin, J. L., & Messina, J. L. (2005) · Endocrinology · doi:10.1210/en.2004-1662 · Cited by 22 · see citing works
Kim, E., Kim, E., Kwon, E., Jang, H.-S., Hur, C., & Choi, M. (2010) · Journal of Medicinal Food · doi:10.1089/jmf.2009.1350 · Cited by 21 · see citing works
Xu, L., & Simoni, R. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(03)00168-1 · Cited by 20 · see citing works
Chen, C., Zhang, S., & Zhang, X.-S. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt712 · Cited by 17 · see citing works
Palaniappan, M., & Menon, K. M. J. (2009) · Biology of Reproduction · doi:10.1095/biolreprod.108.074351 · Cited by 17 · see citing works
Silibinin protects β cells from glucotoxicity through regulation of the Insig-1/SREBP-1c pathway
Chen, K., Zhao, L., He, H., Wan, X., Wang, F., & Mo, Z. (2014) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2014.1883 · Cited by 17 · see citing works
Les oxystérols : métabolisme, rôles biologiques et pathologies associées
Souidi, M., Dubrac, S., Parquet, M., Volle, D. H., Lobaccaro, J. A., Mathé, D., Combes, O., Scanff, P., Lutton, C., & Aigueperse, J. (2004) · Gastroentérologie Clinique et Biologique · doi:10.1016/s0399-8320(04)94919-6 · Cited by 17 · see citing works
Doi, K. (2011) · The Journal of Toxicological Sciences · doi:10.2131/jts.36.695 · Cited by 14 · see citing works
Issandou, M. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.10.012 · Cited by 13 · see citing works
Prakash, J., Mittal, B., Srivastava, A. N., Awasthi, S., Srivastava, P., & Srivastava, N. (2017) · Iranian Biomedical Journal · doi:10.18869/acadpub.ibj.21.4.261 · Cited by 13 · see citing works
Early Transcriptomic Response to OxLDL in Human Retinal Pigment Epithelial Cells
Koirala, D., Beranová-Giorgianni, Š., & Giorgianni, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228818 · Cited by 11 · see citing works
A closed-loop cholesterol shunt controlling experimental dyslipidemia
Unal, G., Xie, Y., & Fussenegger, M. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.08.011 · Cited by 9 · see citing works
An INSIG2 Polymorphism Affects Glucose Homeostasis in Sardinian Obese Children and Adolescents
Zavattari, P., Loche, A., Civolani, P., Pilia, S., Moi, L., Casini, M. R., Minerba, L., & Loche, S. (2010) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2010.00590.x · Cited by 9 · see citing works
Dietary macronutrients, genetic variation, and progression of coronary atherosclerosis among women
Kalantarian, S., Rimm, E. B., Herrington, D. M., & Mozaffarian, D. (2014) · American Heart Journal · doi:10.1016/j.ahj.2014.01.001 · Cited by 8 · see citing works
Cholesterol metabolism in rabbit blastocysts under maternal diabetes
Pendzialek, M., Schindler, M., Plösch, T., Gürke, J., Haucke, E., Hecht, S., Fischer, B., & Santos, A. N. (2016) · Reproduction Fertility and Development · doi:10.1071/rd15542 · Cited by 7 · see citing works
Choi, M.-C., Lee, Y.-U., Kim, S.-H., Lee, J., Park, J., Streb, J. W., Oh, D., Im, S., Kim, T.-Y., Jong, H.-S., et al. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.04.020 · Cited by 7 · see citing works
Microarray analysis of genes in fetal central nervous system after ethylnitrosourea administration
Katayama, K., Ueno, M., Yamauchi, H., Nakayama, H., & Doi, K. (2005) · Birth Defects Research Part B Developmental and Reproductive Toxicology · doi:10.1002/bdrb.20045 · Cited by 6 · see citing works
Mansfield, C. W., Carr, B. R., Faye-Petersen, O. M., Chen, D., Xing, Y., Rainey, W. E., & Parker, C. R. (2011) · Reproductive Sciences · doi:10.1177/1933719111408113 · Cited by 5 · see citing works
Binot, C., & Chouard, C. H. (2018) · Revue Neurologique · doi:10.1016/j.neurol.2017.11.002 · Cited by 5 · see citing works
Synthesis of the enantiomer of the oxysterol-antagonist LY295427
Bielska, A. A., Ory, D. S., & Covey, D. F. (2011) · Steroids · doi:10.1016/j.steroids.2011.03.008 · Cited by 4 · see citing works
Thankan, R. S., Thomas, E. B., Weldemariam, M. M., Purushottamachar, P., Huang, W., Kane, M. A., Zhang, Y., Ambulos, N. P., Wang, B., Weber, D. J., et al. (2025) · Molecular Oncology · doi:10.1002/1878-0261.70009 · Cited by 3 · see citing works
Sabeva, N. S. (2011) · UKnowledge (University of Kentucky) · Cited by 3 · see citing works
Characterisation of cellular defects in Niemann-Pick type C disease
Blom, T. S. (2003) · Työväentutkimus Vuosikirja · Cited by 2 · see citing works
22,23-Epoxides of Sitosterol and Related 7-Oxygenated Δ5-Sterols
Flegentov, G. Y., Tkachev, Y. V., Piir, E. A., Pleshkova, A. P., Timofeev, V. P., & Misharin, A. Y. (2005) · Russian Journal of Bioorganic Chemistry · doi:10.1007/s11171-005-0065-x · Cited by 1 · see citing works
Perfil de la expresión génica de los macrófagos humanos en cultivo en respuesta a atorvastatina
Artieda, M., Cenarro, A., Tejedor, D., Gañán, A., Álvarez, P., Junquera, C., Martínez, A., Pocovı́, M., & Civeira, F. (2004) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/s0214-9168(04)78987-1 · Cited by 1 · see citing works
Bezine, M. (2017) · theses.fr (ABES) · doi:10.70675/a634c389z7b07z4830zb56dzbf7b53a56944 · Cited by 1 · see citing works
The involvement of INSIGs, DGAT1 and APOB in human lipid metabolism
Krapivner, S. (2008) · Figshare
Estudio del factor de transcripción SREBP1 en estados de resistencia a insulina.
Miralles, S. V. (2007) · DIGITAL.CSIC (Spanish National Research Council (CSIC))
The compound LY295427 antagonizes 25-hydroxycholesterol through binding to INSIG
Wen, X.-Y., Zhang, D.-J., He, L.-M., Sun, M., Jiang, Q., Zhu, Y., Song, B.-L., Qiu, W.-W., & Lu, X.-Y. (2026) · Journal of Lipid Research · doi:10.1016/j.jlr.2026.101015
The regulatory role of INSIG1 in testicular Sertoli cells in boars
Zhang, S., Zhou, H., Liu, S., Li, J., Wang, D., Sun, B., Sun, H., & Liang, S. (2026) · Theriogenology · doi:10.1016/j.theriogenology.2026.118087
- Authors
- Janowski, B. A.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Janowski, Bethany A.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-09-19
- Volume
- 99
- Issue
- 20
- Pages
- 12675-12680
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC130519
- OpenAlex
- W1984997497
- Cited by
- 79
- References
- 26
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 1 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 2
- FWCI
- 8.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL20948)
- National Heart, Lung, and Blood Institute (HL-20948, P01HL020948)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- INSIG1, cholesterol homeostasis, oxysterols, SCAP, liver X receptor, hypocholesterolemic agents, SREBP, sterol balance
- MeSH terms
- Anticholesteremic Agents, Cell Line, Cell Nucleus, Cholestanols, Cholesterol, Cloning, Molecular, DNA-Binding Proteins, Gene Expression Regulation, Homeostasis, Humans, Membrane Proteins, Models, Biological, Proteins, RNA, Steroids, Time Factors, Transcription Factors, Transfection, Immunoblotting, Blotting, Northern, Signal Transduction, Up-Regulation, DNA, Complementary, Oligonucleotide Array Sequence Analysis, CCAAT-Enhancer-Binding Proteins, Intracellular Signaling Peptides and Proteins, Sterol Regulatory Element Binding Protein 1
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