SREBP cleavage activating protein


Gene Symbol: SREBP cleavage activating protein
Description: SREBF chaperone
Alias: sterol regulatory element-binding protein cleavage-activating protein, SREBP cleavage-activating protein
Species: human

Top Publications

  1. Iwaki K, Nakajima T, Ota N, Emi M. A common Ile796Val polymorphism of the human SREBP cleavage-activating protein (SCAP) gene. J Hum Genet. 1999;44:421-2 pubmed
    ..The allelic frequencies were: isoleucine (A) allele, 0.57 and valine (G) allele, 0.43. This polymorphism may be useful for genetic studies of disorders affecting intracellular lipid metabolism and hyperlipidemia. ..
  2. Nakajima T, Hamakubo T, Kodama T, Inazawa J, Emi M. Genomic structure and chromosomal mapping of the human sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) gene. J Hum Genet. 1999;44:402-7 pubmed
    ..Our data establish the basis of investigation for molecular variants in this gene that may result in alterations in plasma lipoprotein levels and/or derangement of intracellular lipid metabolism. ..
  3. 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. ..
  4. Hua X, Nohturfft A, Goldstein J, Brown M. Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein. Cell. 1996;87:415-26 pubmed
    ..SCAP appears to be a central regulator of cholesterol metabolism in animal cells...
  5. 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
    ..Our results suggested that the INSIG1 gene was associated with CHD; there might be potential interactive effect on CHD among genes from SREBP2 activating-related pathway; and the SREBP2 gene might be associated with plasma lipid level. ..
  6. Friedlander Y, Schwartz S, Durst R, Meiner V, Robertson A, Erez G, et al. SREBP-2 and SCAP isoforms and risk of early onset myocardial infarction. Atherosclerosis. 2008;196:896-904 pubmed
    ..S. men. The SCAP polymorphism appeared to modify the associations of SREBF-2 genotype with MI risk among men. These novel findings require confirmation in other populations. ..
  7. Sakai J, Nohturfft A, Cheng D, Ho Y, Brown M, Goldstein J. Identification of complexes between the COOH-terminal domains of sterol regulatory element-binding proteins (SREBPs) and SREBP cleavage-activating protein. J Biol Chem. 1997;272:20213-21 pubmed
  8. 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
    ..Our finding is supported by the recent involvement of the INSIG2 gene in obesity in the general population and implicates SREBP-controlled lipogenesis in drug-induced metabolic adverse effects. ..
  9. 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...

More Information


  1. Durst R, Jansen A, Erez G, Bravdo R, Butbul E, Ben Avi L, et al. The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of plasma lipids among familial hypercholesterolaemia patients. Atherosclerosis. 2006;189:443-50 pubmed
    ..Further investigation is needed to confirm this effect. A study in a larger FH group or in non-FH hypercholesterolaemic subjects may further define the role of this regulatory mechanism in determining plasma lipid concentration. ..
  2. Ma K, Ruan X, Powis S, Chen Y, Moorhead J, Varghese Z. Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice. Hepatology. 2008;48:770-81 pubmed publisher
    ..This inhibitory effect may cause cholesterol efflux reduction...
  3. Athippozhy A, Huang L, Wooton Kee C, Zhao T, Jungsuwadee P, Stromberg A, et al. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes. BMC Genomics. 2011;12:95 pubmed publisher
    ..Differential T-Cell signaling in the two most distal regions of the small intestine (ileum and jejunum) was also noted, as well as differential expression of transporters that likely play a key role in nutrient uptake. ..
  4. Yang Y, Lin Y, Duan X, Lv H, Xing W, Li Q, et al. The effects of cell death-inducing DNA fragmentation factor-?-like effector C (CIDEC) on milk lipid synthesis in mammary glands of dairy cows. J Dairy Sci. 2017;100:4014-4024 pubmed publisher
    ..acyltransferase 1 (DGAT1, -60%), sterol regulatory element-binding protein 1 (SREBP1, -45%), and SREBP cleavage activating protein (SCAP, -66%)...
  5. Wu Y, Ma K, Zhang Y, Wen Y, Wang G, Hu Z, et al. Lipid disorder and intrahepatic renin-angiotensin system activation synergistically contribute to non-alcoholic fatty liver disease. Liver Int. 2016;36:1525-34 pubmed publisher
    ..These findings demonstrate that lipid disorder and intrahepatic RAS activation synergistically accelerate NAFLD progression. ..
  6. Besnard V, Xu Y, Whitsett J. Sterol response element binding protein and thyroid transcription factor-1 (Nkx2.1) regulate Abca3 gene expression. Am J Physiol Lung Cell Mol Physiol. 2007;293:L1395-405 pubmed
    ..Abca3 gene expression is mediated by discrete cis-acting cassettes that mediate pulmonary cell- and lipid-sensitive pathways regulating surfactant homeostasis...
  7. Dong Q, Giorgianni F, Beranova Giorgianni S, Deng X, O Meally R, Bridges D, et al. Glycogen synthase kinase-3-mediated phosphorylation of serine 73 targets sterol response element binding protein-1c (SREBP-1c) for proteasomal degradation. Biosci Rep. 2015;36:e00284 pubmed publisher
    ..We propose that GSK-3-mediated phosphorylation of serine 73 in the rat SREBP-1c and its concomitant destabilization represents a novel mechanism involved in the inhibition of de novo lipid synthesis in the liver. ..
  8. Zhang Y, Ma K, Liu J, Wu Y, Hu Z, Liu L, et al. Dysregulation of low-density lipoprotein receptor contributes to podocyte injuries in diabetic nephropathy. Am J Physiol Endocrinol Metab. 2015;308:E1140-8 pubmed publisher
    ..High glucose disrupted LDLr feedback regulation in podocytes, which may cause intracellular lipid accumulation and alteration of podocyte phenotype, thereby accelerating DN progression. ..
  9. Xu Z, Li J, Dong X, Tan Z, Wu W, Xie Q, et al. Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE-/- Mice through the ROS/MAPK/NF-κB Pathway. Nutrients. 2015;7:7085-105 pubmed publisher
    ..Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis. ..
  10. Romani P, Brian I, Santinon G, Pocaterra A, Audano M, Pedretti S, et al. Extracellular matrix mechanical cues regulate lipid metabolism through Lipin-1 and SREBP. Nat Cell Biol. 2019;21:338-347 pubmed publisher
    ..We thus identify a general mechanism centered on Lipin-1 and SREBP that links the physical cell microenvironment to a key metabolic pathway. ..
  11. Ma K, Liu L, Zhang Y, Wang G, Hu Z, Chen P, et al. Aspirin attenuates podocyte injury in diabetic rats through overriding cyclooxygenase-2-mediated dysregulation of LDL receptor pathway. Int Urol Nephrol. 2019;51:551-558 pubmed publisher
    ..However, when COX-2 expression was inhibited by aspirin, these changes in the DM rats were significantly attenuated. Aspirin attenuates podocyte injury in DN, which may be through COX-2-mediated dysregulation of LDLr pathway. ..
  12. Kanimozhi V, Palanivel K, Akbarsha M, Kadalmani B. Molecular Mechanisms of Tributyltin-Induced Alterations in Cholesterol Homeostasis and Steroidogenesis in Hamster Testis: In Vivo and In Vitro Studies. J Cell Biochem. 2017;: pubmed publisher
    ..Therefore, ApoE is one of the important molecular targets that can be intercepted in context of male infertility / male contraception. This article is protected by copyright. All rights reserved...
  13. Aydin S, Sahin F. Stem Cells Derived from Dental Tissues. Adv Exp Med Biol. 2019;: pubmed publisher
  14. Xu T, Tao H, Chang G, Zhang K, Xu L, Shen X. Lipopolysaccharide derived from the rumen down-regulates stearoyl-CoA desaturase 1 expression and alters fatty acid composition in the liver of dairy cows fed a high-concentrate diet. BMC Vet Res. 2015;11:52 pubmed publisher
    ..the expression of sterol regulatory element binding transcription factors (SREBF1c, SREBF2) and SREBP cleavage activating protein (SCAP) was down-regulated, while peroxisome proliferator-activated receptor α (PPARα) was up-..
  15. Ahn S, Martin R, Rao S, Choi M. Neuropeptides predicted from the transcriptome analysis of the gray garden slug Deroceras reticulatum. Peptides. 2017;93:51-65 pubmed publisher
  16. Yu G, Wang J, Lin X, Diao S, Cao Y, Dong R, et al. Demethylation of SFRP2 by histone demethylase KDM2A regulated osteo-/dentinogenic differentiation of stem cells of the apical papilla. Cell Prolif. 2016;49:330-40 pubmed publisher
    ..Our results have identified a new function of SFRP2 and shed new light on the molecular mechanism underlying directed differentiation of stem cells of dental origin. ..
  17. Inoue J, Miyata S, Shimizu M, Sato R. Isoxanthohumol stimulates ubiquitin-proteasome-dependent degradation of precursor forms of sterol regulatory element-binding proteins. Biosci Biotechnol Biochem. 2018;82:1591-1598 pubmed publisher
  18. Tarling E, Ahn H, de Aguiar Vallim T. The nuclear receptor FXR uncouples the actions of miR-33 from SREBP-2. Arterioscler Thromb Vasc Biol. 2015;35:787-95 pubmed publisher
    ..Further, we conclude that the FXR agonist-dependent increase in miR-33 requires transcription of the Srebp-2 gene. ..
  19. Chang H, Chang M, Wu I, Huang G, Huang W, Wang Y, et al. Role of ALK5/Smad2/3 and MEK1/ERK Signaling in Transforming Growth Factor Beta 1-modulated Growth, Collagen Turnover, and Differentiation of Stem Cells from Apical Papilla of Human Tooth. J Endod. 2015;41:1272-80 pubmed publisher
    ..These results highlight the future use of TGF-β1 and SCAP for engineering of pulpal regeneration and apexogenesis. ..
  20. Diao S, Yang D, Dong R, Wang L, Wang J, Du J, et al. Enriched trimethylation of lysine 4 of histone H3 of WDR63 enhanced osteogenic differentiation potentials of stem cells from apical papilla. J Endod. 2015;41:205-11 pubmed publisher
    ..These results indicate that WDR63 is a positive enhancer for SCAP osteogenic differentiation and suggest that activation of WDR63 signaling might improve tissue regeneration mediated by MSCs of dental origin. ..
  21. Hashimoto M, Kobayashi K, Yamazaki M, Kazuki Y, Takehara S, Oshimura M, et al. Cyp3a deficiency enhances androgen receptor activity and cholesterol synthesis in the mouse prostate. J Steroid Biochem Mol Biol. 2016;163:121-8 pubmed publisher
  22. 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
    ..Overall, changes in potential antilipogenic FA and mRNA abundance of candidate lipogenic genes support a relationship between them and suggest that FO-induced MFD in dairy ewes would be mediated by transcriptional mechanisms. ..
  23. 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
  24. Bergeron F, Nadeau G, Viger R. GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway. Reproduction. 2015;149:245-57 pubmed publisher
    ..These data therefore provide strong evidence that GATA4 is an essential transcription factor that sits atop of the Leydig cell steroidogenic program. ..
  25. Howarth D, Yin C, Yeh K, Sadler K. Defining hepatic dysfunction parameters in two models of fatty liver disease in zebrafish larvae. Zebrafish. 2013;10:199-210 pubmed publisher
    ..This study provides a panel of parameters to assess liver disease that can be easily applied to zebrafish mutants, transgenics, and for drug screening in which liver function is an important consideration. ..
  26. 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
    ..Overall, the data provide strong support for a central role of SREBP1 in the regulation of milk fat synthesis in goat mammary cells. ..
  27. Li N, Zhou Z, Shen Y, Xu J, Miao H, Xiong Y, et al. Inhibition of the sterol regulatory element-binding protein pathway suppresses hepatocellular carcinoma by repressing inflammation in mice. Hepatology. 2017;65:1936-1947 pubmed publisher
    ..This study identifies a previously underappreciated role of the SREBP pathway in HCC and suggests a novel metabolic strategy to control liver cancer. (Hepatology 2017;65:1936-1947). ..
  28. Shao W, Espenshade P. Sterol regulatory element-binding protein (SREBP) cleavage regulates Golgi-to-endoplasmic reticulum recycling of SREBP cleavage-activating protein (SCAP). J Biol Chem. 2014;289:7547-57 pubmed publisher
    ..However, we show that SREBP actively prevents premature recycling of SCAP-SREBP until initiation of SREBP cleavage. SREBP regulates SCAP in human cells and yeast, indicating that this is an ancient regulatory mechanism. ..
  29. Soufi M, Ruppert V, Kurt B, Schaefer J. The impact of severe LDL receptor mutations on SREBP-pathway regulation in homozygous familial hypercholesterolemia (FH). Gene. 2012;499:218-22 pubmed publisher
    ..Gene expression experiments with LDL receptor lacking primary FH fibroblasts, revealed that SR-BI and ABCA1 are important regulators for cholesterol acquisition in FH cells, consistent with findings in cells from NPC and TD patients...
  30. Engelking L, Cantoria M, Xu Y, Liang G. Developmental and extrahepatic physiological functions of SREBP pathway genes in mice. Semin Cell Dev Biol. 2018;81:98-109 pubmed publisher
    ..The findings reviewed herein provide a blueprint to guide future studies defining the complex interactions between lipid biology and the physiologic processes of many distinct organ systems. ..
  31. 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
    ..475-2.193, P = 6.61 × 10(-9)). We identified interaction of three genes in INSIG-SCAP-SREBP pathway on risk of obesity, revealing that these genes affect obesity more likely through a complex interaction pattern than single gene effect. ..
  32. Shao W, Machamer C, Espenshade P. Fatostatin blocks ER exit of SCAP but inhibits cell growth in a SCAP-independent manner. J Lipid Res. 2016;57:1564-73 pubmed publisher
    ..b>SREBP cleavage activating protein (SCAP) plays an essential role in SREBP activation by mediating endoplasmic reticulum (ER)-to-Golgi ..
  33. Irisawa M, Inoue J, Ozawa N, Mori K, Sato R. The sterol-sensing endoplasmic reticulum (ER) membrane protein TRC8 hampers ER to Golgi transport of sterol regulatory element-binding protein-2 (SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2 cleavage. J Biol Chem. 2009;284:28995-9004 pubmed publisher
  34. Scott M, Zilinski G, Kirkpatrick T, Himel V, Sabey K, Lallier T. The Effects of Irrigants on the Survival of Human Stem Cells of the Apical Papilla, Including Endocyn. J Endod. 2017;: pubmed publisher
  35. Javitt N. Cholesterol, hydroxycholesterols, and bile acids. Biochem Biophys Res Commun. 2002;292:1147-53 pubmed
    ..Precisely when the proportions contributed by these two metabolic pathways to bile acid synthesis begin to shift and the role of the cholesterol 27-hydroxylase pathway in reverse cholesterol transport mandate further study. ..
  36. Matsuzaki Y, Besnard V, Clark J, Xu Y, Wert S, Ikegami M, et al. STAT3 regulates ABCA3 expression and influences lamellar body formation in alveolar type II cells. Am J Respir Cell Mol Biol. 2008;38:551-8 pubmed
    ..ABCA3 expression is regulated by IL-6 in a pathway that includes STAT3, PI3K, AKT, SCAP, and SREBP. Activation of STAT3 after exposure to IL-6 enhances ABCA3 expression, which, in turn, influences pulmonary surfactant homeostasis...
  37. 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. ..
  38. Prabhu A, Krycer J, Brown A. Overexpression of a key regulator of lipid homeostasis, Scap, promotes respiration in prostate cancer cells. FEBS Lett. 2013;587:983-8 pubmed publisher
    ..This striking observation warrants further investigation. Given that SREBP-2 and Scap are regulated by factors driving prostate growth, exploring this observation further could shed light on prostate carcinogenesis. ..
  39. Gao Y, Lee C, Song J, Li S, Cui Y, Liu Y, et al. Digenic mutations on SCAP and AGXT2 predispose to premature myocardial infarction. Oncotarget. 2017;8:100141-100149 pubmed publisher
    ..This study indicates that SCAP and AGXT2 are potential causative genes for PMI. Digenic mutation carriers may manifest a more severe phenotype, namely premature MI...
  40. Rader D. A new feature on the cholesterol-lowering landscape. Nat Med. 2001;7:1282-4 pubmed
  41. 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. ..
  42. 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. ..
  43. Nieminen T, Matinheikki J, Nenonen A, Kukkonen Harjula K, Lindi V, Hämelahti P, et al. The relationship of sterol regulatory element-binding protein cleavage-activation protein and apolipoprotein E gene polymorphisms with metabolic changes during weight reduction. Metabolism. 2007;56:876-80 pubmed
    ..However, the apo E-but not SCAP genotype-seems to be one of the modifying factors for serum cholesterol concentrations during very low-energy diet in obese premenopausal women. ..
  44. Yang Y, Song J, Wang S, Liu F, Zhang Y, Shang X, et al. Genetic variations in sterol regulatory element binding protein cleavage-activating protein (SCAP) are associated with blood pressure in overweight/obese Chinese children. PLoS ONE. 2017;12:e0177973 pubmed publisher
    ..50, 95%CI: 1.10-2.05; P = 0.01). This study demonstrated that SCAP rs12487736 and rs12490383 were significantly associated with SBP and SHBP in overweight/obese Chinese children. It provided the evidence for association of SCAP with SBP. ..
  45. Asano L, Watanabe M, Ryoden Y, Usuda K, Yamaguchi T, Khambu B, et al. Vitamin D Metabolite, 25-Hydroxyvitamin D, Regulates Lipid Metabolism by Inducing Degradation of SREBP/SCAP. Cell Chem Biol. 2017;24:207-217 pubmed publisher
    ..The present results suggest a previously unrecognized molecular mechanism of vitamin D-mediated lipid control that might be useful in the treatment of metabolic diseases. ..
  46. Tseng M, Amin B, Barmettler A. Eyelid syringocystadenoma papilliferum: A novel presentation with major review. Orbit. 2017;:1-4 pubmed publisher
  47. Chen C, Hsu L, Huang K, Goto S, Chen C, Nakano T. Overexpression of Insig-2 inhibits atypical antipsychotic-induced adipogenic differentiation and lipid biosynthesis in adipose-derived stem cells. Sci Rep. 2017;7:10901 pubmed publisher
    ..Such abnormal lipogenesis can be reversed when Insig-2 expression was increased, suggesting that Insig/SCAP/SREBP signaling may be a therapeutic target for AAP-induced weight gain and metabolic abnormalities. ..
  48. Viswanath A, Vanacker J, Germain L, Leprince J, Diogenes A, Shakesheff K, et al. Extracellular matrix-derived hydrogels for dental stem cell delivery. J Biomed Mater Res A. 2017;105:319-328 pubmed publisher
    ..2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 319-328, 2017...
  49. 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. ..
  50. Yadlapati M, Biguetti C, Cavalla F, Nieves F, Bessey C, Bohluli P, et al. Characterization of a Vascular Endothelial Growth Factor-loaded Bioresorbable Delivery System for Pulp Regeneration. J Endod. 2017;43:77-83 pubmed publisher
    ..Our results show that the VF used in this study is biocompatible and may be a promising scaffold for additional optimization and use in endodontic regenerative procedures. ..
  51. Yang X, Wu F, Chen J, Wang C, Zhu Y, Li F, et al. GP73 regulates Hepatic Steatosis by enhancing SCAP-SREBPs interaction. Sci Rep. 2017;7:14932 pubmed publisher
    ..Our findings revealed previously unrecognized role of GP73 in lipid metabolism. ..
  52. Fan Y, Karhunen P, Levula M, Ilveskoski E, Mikkelsson J, Kajander O, et al. Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death. Thromb J. 2008;6:17 pubmed publisher
    ..The results suggest that the allelic variants (SREBF-2 1784G>C and SCAP 2386A>G) in the cholesterol homeostasis regulating SREBF-SCAP pathway may contribute to SCD in early middle-aged men. ..
  53. Grand Perret T, Bouillot A, Perrot A, Commans S, Walker M, Issandou M. SCAP ligands are potent new lipid-lowering drugs. Nat Med. 2001;7:1332-8 pubmed
    ..These findings have led to the identification of a class of compounds that represent a promising new class of hypolipidemic drugs. ..
  54. Zhang L, Rajbhandari P, Priest C, Sandhu J, Wu X, TEMEL R, et al. Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP. elife. 2017;6: pubmed publisher
    ..These findings define an additional mechanism linking hepatic sterol levels to the reciprocal actions of the SREBP-2 and LXR pathways. ..
  55. 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...
  56. Liu H, Zhang L, Sun J, Chen W, Li S, Wang Q, et al. Endoplasmic Reticulum Protein SCAP Inhibits Dengue Virus NS2B3 Protease by Suppressing Its K27-Linked Polyubiquitylation. J Virol. 2017;91: pubmed publisher
    ..Both of these functions protect STING from being cleaved by the NS2B3 protease and thus contribute to host antiviral response. ..
  57. Zheng Z, Zhou Y, Zhang X, Thu P, Xie Z, Lu C, et al. Anhydroicaritin improves diet-induced obesity and hyperlipidemia and alleviates insulin resistance by suppressing SREBPs activation. Biochem Pharmacol. 2016;122:42-61 pubmed publisher
    ..Thus, AHI can serve as a leading compound for pharmacological control of metabolic diseases. ..
  58. El Ayachi I, Zhang J, Zou X, Yu Z, Wei W, O Connell K, et al. Human dental stem cell derived transgene-free iPSCs generate functional neurons via embryoid body-mediated and direct induction methods. J Tissue Eng Regen Med. 2017;: pubmed publisher
    ..Thus, TF-DSC iPSCs are capable of undergoing guided neurogenic differentiation into functional neurons in vitro, thereby may serve as a cell source for neural regeneration...
  59. Kumar A, Kumar V, Rattan V, Jha V, Pal A, Bhattacharyya S. Molecular spectrum of secretome regulates the relative hepatogenic potential of mesenchymal stem cells from bone marrow and dental tissue. Sci Rep. 2017;7:15015 pubmed publisher
    ..To the best of our knowledge, this is the first study regarding detailed investigation of hepatogenic potential of BMSCs v/s DMSCs (DPSC, SCAP & DFSC) along-with secretome characterization. ..
  60. Eskander M, Takimoto K, Diogenes A. Evaluation of mesenchymal stem cell modulation of trigeminal neuronal responses to cold. Neuroscience. 2017;360:61-67 pubmed publisher
    ..Co-culture with SCAP significantly increased sustained ATP-evoked inward current density (p<0.05). These data suggest that SCAP release trophic factors that act on afferent neurons to enhance cold-sensitive ion channel activity. ..
  61. Chen Z, Ding Z, Ma G, Liu N, Qian Q. Sterol regulatory element-binding transcription factor (SREBF)-2, SREBF cleavage-activating protein (SCAP), and premature coronary artery disease in a Chinese population. Mol Biol Rep. 2011;38:2895-901 pubmed publisher
    ..05). We could not identify any association between these two SNPs and premature CAD or extent of coronary lesions in a Chinese population. ..
  62. Yang L, Chen J, Li Y, Wang Y, Liang S, Shi Y, et al. Association between SCAP and SREBF1 gene polymorphisms and metabolic syndrome in schizophrenia patients treated with atypical antipsychotics. World J Biol Psychiatry. 2016;17:467-74 pubmed publisher
    ..026, OR =2.37, 95% CI: 1.3 6-4.12). SCAP polymorphisms with drug-induced MetS were negative in this study. The genetic polymorphisms of SREBF1 could play a role in the mechanism for interindividual variation of AAP-induced MetS. ..
  63. Friedman B, Sahu J, Solomides C, Connolly D, Lee J. Contiguous verrucous proliferations in syringocystadenoma papilliferum: a retrospective analysis with additional evaluation via mutation-specific BRAF V600E immunohistochemistry. J Cutan Pathol. 2017;: pubmed publisher
    ..sup>4,5,6 The tumor has a varied clinical appearance, but typically presents as a raised warty, hairless plaque or nodule.3...
  64. Jensen K, Tadin Strapps M, Wang S, Hubert J, Kan Y, Ma Y, et al. Dose-dependent effects of siRNA-mediated inhibition of SCAP on PCSK9, LDLR, and plasma lipids in mouse and rhesus monkey. J Lipid Res. 2016;57:2150-2162 pubmed
    ..In conclusion, siRNA-mediated inhibition of SCAP resulted in a significant reduction in circulating PCSK9 and LDL-C in rodent and primate models supporting SCAP as a novel target for the treatment of dyslipidemia. ..
  65. Papazyan R, Sun Z, Kim Y, Titchenell P, Hill D, Lu W, et al. Physiological Suppression of Lipotoxic Liver Damage by Complementary Actions of HDAC3 and SCAP/SREBP. Cell Metab. 2016;24:863-874 pubmed publisher
    ..Here we show that inactivation of SREBP by hepatic deletion of SREBP cleavage activating protein (SCAP) abrogates the increase in lipogenesis caused by loss of HDAC3, but fatty acid oxidation ..
  66. Vallés J, Diaz E, Martín Loeches I, Bacelar N, Saludes P, Lema J, et al. Evolution over a 15-year period of the clinical characteristics and outcomes of critically ill patients with severe community-acquired pneumonia. Med Intensiva. 2016;40:238-45 pubmed publisher
    ..The increased use of combined antibiotic therapy and the decreasing rates of bacteremia were associated to improved patient prognosis. ..
  67. Gao Y, Zhou Y, Goldstein J, Brown M, Radhakrishnan A. Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis. J Biol Chem. 2017;292:8729-8737 pubmed publisher
    ..These insights suggest a new structural model for cholesterol-mediated regulation of Scap activity. ..
  68. Sun S, Wang M, Song H, Wu T, Wei H, He S, et al. SCAP gene polymorphisms decrease the risk of nonalcoholic fatty liver disease in females with metabolic syndrome. J Genet. 2013;92:565-70 pubmed
  69. Williams K, Argus J, Zhu Y, Wilks M, Marbois B, York A, et al. An essential requirement for the SCAP/SREBP signaling axis to protect cancer cells from lipotoxicity. Cancer Res. 2013;73:2850-62 pubmed publisher
    ..These studies highlight the importance of fatty acid desaturation in cancer growth and provide a novel mechanistic explanation for the role of SREBPs in cancer metabolism. ..
  70. Yang L, Chen D. [Effects of TNF alpha on the expression of SCAP and triglyceride contents in cultured steatotic hepatocytes]. Zhonghua Gan Zang Bing Za Zhi. 2007;15:767-70 pubmed
    ..35) mg/10(7) cells, F1(13.36+/-1.99) mg/10(7) cells, F = 82.94]. TNF alpha upregulates the expression of SCAP and promotes the synthesis of triglyceride; it probably participates in the process of developing steatosis of hepatocytes. ..
  71. Wang W, Liu W, Durnaoglu S, Lee S, Lian J, Lehner R, et al. Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis. Sci Rep. 2017;7:5941 pubmed publisher
    ..We propose that ER Ca2+ status is an important determinant of the basal sensitivity of the sterol sensing mechanism inherent to the SREBP processing pathway. ..
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    ..They indicate that insect cells can respond to sterols when proper regulatory proteins are expressed. ..
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    ..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. ..
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    ..The common membrane topology of the two proteins is consistent with the notion that sterols regulate both proteins by a common mechanism...