Sterol regulatory element-binding proteins (SREBPs) are membrane-bound proteins that act as transcription factors. They regulate lipid, especially cholesterol, biosynthesis and uptake at a transcriptional level to maintain cellular lipid homeostasis. In addition, SREBP appears to be involved in a variety of other cellular processes. This pathway of SREBP focusses on the regulation of lipid metabolism by SREBP. The data on which this pathway is based, is derived from a variety of in vitro and in vivo studies using different species, including mouse, rat, hamster and human.
This pathway served as the basis for a review about SREBP that was published in Genes and Nutrition: PubMed.
Comments
HomologyConvert
This pathway was inferred from Homo sapiens pathway WP1982(79943) with a 99.0% conversion rate.
Yellaturu CR, Deng X, Cagen LM, Wilcox HG, Mansbach CM 2nd, Siddiqi SA, Park EA, Raghow R, Elam MB; ''Insulin enhances post-translational processing of nascent SREBP-1c by promoting its phosphorylation and association with COPII vesicles.''; J Biol Chem, 2009 PubMedEurope PMCScholia
Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A, Boss O, Hirsch ML, Ribich S, Smith JJ, Israelian K, Westphal CH, Rodgers JT, Shioda T, Elson SL, Mulligan P, Najafi-Shoushtari H, Black JC, Thakur JK, Kadyk LC, Whetstine JR, Mostoslavsky R, Puigserver P, Li X, Dyson NJ, Hart AC, Nأ¤أ¤r AM; ''Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP.''; Genes Dev, 2010 PubMedEurope PMCScholia
Radhakrishnan A, Ikeda Y, Kwon HJ, Brown MS, Goldstein JL; ''Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig.''; Proc Natl Acad Sci U S A, 2007 PubMedEurope PMCScholia
Matsuda M, Korn BS, Hammer RE, Moon YA, Komuro R, Horton JD, Goldstein JL, Brown MS, Shimomura I; ''SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation.''; Genes Dev, 2001 PubMedEurope PMCScholia
Peterson TR, Sengupta SS, Harris TE, Carmack AE, Kang SA, Balderas E, Guertin DA, Madden KL, Carpenter AE, Finck BN, Sabatini DM; ''mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway.''; Cell, 2011 PubMedEurope PMCScholia
Bennett MK, Ngo TT, Athanikar JN, Rosenfeld JM, Osborne TF; ''Co-stimulation of promoter for low density lipoprotein receptor gene by sterol regulatory element-binding protein and Sp1 is specifically disrupted by the yin yang 1 protein.''; J Biol Chem, 1999 PubMedEurope PMCScholia
Yang F, Vought BW, Satterlee JS, Walker AK, Jim Sun ZY, Watts JL, DeBeaumont R, Saito RM, Hyberts SG, Yang S, Macol C, Iyer L, Tjian R, van den Heuvel S, Hart AC, Wagner G, Nأ¤أ¤r AM; ''An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis.''; Nature, 2006 PubMedEurope PMCScholia
Bengoechea-Alonso MT, Ericsson J; ''A phosphorylation cascade controls the degradation of active SREBP1.''; J Biol Chem, 2009 PubMedEurope PMCScholia
Takeuchi Y, Yahagi N, Izumida Y, Nishi M, Kubota M, Teraoka Y, Yamamoto T, Matsuzaka T, Nakagawa Y, Sekiya M, Iizuka Y, Ohashi K, Osuga J, Gotoda T, Ishibashi S, Itaka K, Kataoka K, Nagai R, Yamada N, Kadowaki T, Shimano H; ''Polyunsaturated fatty acids selectively suppress sterol regulatory element-binding protein-1 through proteolytic processing and autoloop regulatory circuit.''; J Biol Chem, 2010 PubMedEurope PMCScholia
Inoue J, Ito Y, Shimada S, Satoh SI, Sasaki T, Hashidume T, Kamoshida Y, Shimizu M, Sato R; ''Glutamine stimulates the gene expression and processing of sterol regulatory element binding proteins, thereby increasing the expression of their target genes.''; FEBS J, 2011 PubMedEurope PMCScholia
Sun LP, Li L, Goldstein JL, Brown MS; ''Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro.''; J Biol Chem, 2005 PubMedEurope PMCScholia
Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS; ''SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene.''; Cell, 1993 PubMedEurope PMCScholia
Dif N, Euthine V, Gonnet E, Laville M, Vidal H, Lefai E; ''Insulin activates human sterol-regulatory-element-binding protein-1c (SREBP-1c) promoter through SRE motifs.''; Biochem J, 2006 PubMedEurope PMCScholia
Ericsson J, Usheva A, Edwards PA; ''YY1 is a negative regulator of transcription of three sterol regulatory element-binding protein-responsive genes.''; J Biol Chem, 1999 PubMedEurope PMCScholia
Lee JN, Zhang X, Feramisco JD, Gong Y, Ye J; ''Unsaturated fatty acids inhibit proteasomal degradation of Insig-1 at a postubiquitination step.''; J Biol Chem, 2008 PubMedEurope PMCScholia
Rottiers V, Nأ¤أ¤r AM; ''MicroRNAs in metabolism and metabolic disorders.''; Nat Rev Mol Cell Biol, 2012 PubMedEurope PMCScholia
Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M; ''AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice.''; Cell Metab, 2011 PubMedEurope PMCScholia
Lee JN, Song B, DeBose-Boyd RA, Ye J; ''Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78.''; J Biol Chem, 2006 PubMedEurope PMCScholia
Uttarwar L, Gao B, Ingram AJ, Krepinsky JC; ''SREBP-1 Activation by Glucose Mediates TGFخ² Upregulation in Mesangial Cells.''; Am J Physiol Renal Physiol, 2011 PubMedEurope PMCScholia
Sato R; ''Sterol metabolism and SREBP activation.''; Arch Biochem Biophys, 2010 PubMedEurope PMCScholia
Hao J, Liu S, Zhao S, Liu Q, Lv X, Chen H, Niu Y, Duan H; ''PI3K/Akt pathway mediates high glucose-induced lipogenesis and extracellular matrix accumulation in HKC cells through regulation of SREBP-1 and TGF-خ²1.''; Histochem Cell Biol, 2011 PubMedEurope PMCScholia
Engelking LJ, Kuriyama H, Hammer RE, Horton JD, Brown MS, Goldstein JL, Liang G; ''Overexpression of Insig-1 in the livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis.''; J Clin Invest, 2004 PubMedEurope PMCScholia
Zhang Y, Lei T, Huang JF, Wang SB, Zhou LL, Yang ZQ, Chen XD; ''The link between fibroblast growth factor 21 and sterol regulatory element binding protein 1c during lipogenesis in hepatocytes.''; Mol Cell Endocrinol, 2011 PubMedEurope PMCScholia
Brown MS, Goldstein JL; ''A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood.''; Proc Natl Acad Sci U S A, 1999 PubMedEurope PMCScholia
Yamamoto T, Shimano H, Inoue N, Nakagawa Y, Matsuzaka T, Takahashi A, Yahagi N, Sone H, Suzuki H, Toyoshima H, Yamada N; ''Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver.''; J Biol Chem, 2007 PubMedEurope PMCScholia
Jeon TI, Osborne TF; ''SREBPs: metabolic integrators in physiology and metabolism.''; Trends Endocrinol Metab, 2012 PubMedEurope PMCScholia
Ruderman NB, Xu XJ, Nelson L, Cacicedo JM, Saha AK, Lan F, Ido Y; ''AMPK and SIRT1: a long-standing partnership?''; Am J Physiol Endocrinol Metab, 2010 PubMedEurope PMCScholia
Sakai J, Nohturfft A, Goldstein JL, Brown MS; ''Cleavage of sterol regulatory element-binding proteins (SREBPs) at site-1 requires interaction with SREBP cleavage-activating protein. Evidence from in vivo competition studies.''; J Biol Chem, 1998 PubMedEurope PMCScholia
Zhao X, Feng D, Wang Q, Abdulla A, Xie XJ, Zhou J, Sun Y, Yang ES, Liu LP, Vaitheesvaran B, Bridges L, Kurland IJ, Strich R, Ni JQ, Wang C, Ericsson J, Pessin JE, Ji JY, Yang F; ''Regulation of lipogenesis by cyclin-dependent kinase 8-mediated control of SREBP-1.''; J Clin Invest, 2012 PubMedEurope PMCScholia
Gong Y, Lee JN, Lee PC, Goldstein JL, Brown MS, 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 PubMedEurope PMCScholia
Owen JL, Zhang Y, Bae SH, Farooqi MS, Liang G, Hammer RE, Goldstein JL, Brown MS; ''Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase.''; Proc Natl Acad Sci U S A, 2012 PubMedEurope PMCScholia
Dأ¼vel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, Vander Heiden MG, MacKeigan JP, Finan PM, Clish CB, Murphy LO, Manning BD; ''Activation of a metabolic gene regulatory network downstream of mTOR complex 1.''; Mol Cell, 2010 PubMedEurope PMCScholia
Yellaturu CR, Deng X, Park EA, Raghow R, Elam MB; ''Insulin enhances the biogenesis of nuclear sterol regulatory element-binding protein (SREBP)-1c by posttranscriptional down-regulation of Insig-2A and its dissociation from SREBP cleavage-activating protein (SCAP).SREBP-1c complex.''; J Biol Chem, 2009 PubMedEurope PMCScholia
Chen G, Liang G, Ou J, Goldstein JL, Brown MS; ''Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver.''; Proc Natl Acad Sci U S A, 2004 PubMedEurope PMCScholia
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 PubMedEurope PMCScholia
Xia M, Liu Y, Guo H, Wang D, Wang Y, Ling W; ''Retinol binding protein 4 stimulates hepatic SREBP-1 and increases lipogenesis through PGC-1beta-dependent pathway.''; Hepatology, 2013 PubMedEurope PMCScholia
Lin J, Yang R, Tarr PT, Wu PH, Handschin C, Li S, Yang W, Pei L, Uldry M, Tontonoz P, Newgard CB, Spiegelman BM; ''Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP.''; Cell, 2005 PubMedEurope PMCScholia
Daemen S, Kutmon M, Evelo CT; ''A pathway approach to investigate the function and regulation of SREBPs.''; Genes Nutr, 2013 PubMedEurope PMCScholia
Nagoshi E, Imamoto N, Sato R, Yoneda Y; ''Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip.''; Mol Biol Cell, 1999 PubMedEurope PMCScholia
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