Sterol regulatory element-binding proteins (SREBP) signaling (Homo sapiens)
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Description
Sterol regulatory element-binding protein (SREBP) are membrane-bound proteins that act as transcription factors. They regulate cholesterol biosynthesis and uptake, at a transcriptional level, to maintain cellular cholesterol homeostasis.
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- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- Rottiers V, Näär AM; ''MicroRNAs in metabolism and metabolic disorders.''; Nat Rev Mol Cell Biol, 2012 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- Ye J, Davé UP, Grishin NV, Goldstein JL, Brown MS; ''Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease.''; Proc Natl Acad Sci U S A, 2000 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- Krycer JR, Sharpe LJ, Luu W, Brown AJ; ''The Akt-SREBP nexus: cell signaling meets lipid metabolism.''; Trends Endocrinol Metab, 2010 PubMed Europe PMC Scholia
- Zeng L, Lu M, Mori K, Luo S, Lee AS, Zhu Y, Shyy JY; ''''; , PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- Daemen S, Kutmon M, Evelo CT; ''A pathway approach to investigate the function and regulation of SREBPs.''; Genes Nutr, 2013 PubMed Europe PMC Scholia
- Shimano H; ''Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes.''; Prog Lipid Res, 2001 PubMed Europe PMC Scholia
- Adams CM, Reitz J, De Brabander JK, Feramisco JD, Li L, Brown MS, Goldstein JL; ''Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs.''; J Biol Chem, 2004 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- Radhakrishnan A, McConnell HM; ''Chemical activity of cholesterol in membranes.''; Biochemistry, 2000 PubMed Europe PMC Scholia
- Ponugoti B, Kim DH, Xiao Z, Smith Z, Miao J, Zang M, Wu SY, Chiang CM, Veenstra TD, Kemper JK; ''SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism.''; J Biol Chem, 2010 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- Sato R; ''Sterol metabolism and SREBP activation.''; Arch Biochem Biophys, 2010 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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, Näär AM; ''An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis.''; Nature, 2006 PubMed Europe PMC Scholia
- Jeon TI, Osborne TF; ''SREBPs: metabolic integrators in physiology and metabolism.''; Trends Endocrinol Metab, 2012 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- Defour A, Dessalle K, Castro Perez A, Poyot T, Castells J, Gallot YS, Durand C, Euthine V, Gu Y, Béchet D, Peinnequin A, Lefai E, Freyssenet D; ''Sirtuin 1 regulates SREBP-1c expression in a LXR-dependent manner in skeletal muscle.''; PLoS One, 2012 PubMed Europe PMC Scholia
- 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, Näär AM; ''Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP.''; Genes Dev, 2010 PubMed Europe PMC Scholia
- Düvel 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
- Bengoechea-Alonso MT, Ericsson J; ''A phosphorylation cascade controls the degradation of active SREBP1.''; J Biol Chem, 2009 PubMed Europe PMC Scholia
- 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 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
AKT | GeneProduct | ENSG00000142208 (Ensembl Human) | |
ARC | Complex | activator recruited cofactor (ARC)-mediator activator complex | |
ATF6 | GeneProduct | ENSG00000118217 (Ensembl Human) | |
ATP citrate lyase | GeneProduct | ENSG00000131473 (Ensembl Human) | |
Acyl-CoA binding protein | GeneProduct | ENSG00000155368 (Ensembl Human) | |
CDK8 | GeneProduct | ENSG00000132964 (Ensembl Human) | |
CREB | GeneProduct | ENSG00000118260 (Ensembl Human) | |
Cholesterol | Metabolite | HMDB00067 (HMDB) | |
GSK3 | GeneProduct | ENSG00000105723 (Ensembl Human) | |
Glucose | Metabolite | HMDB00122 (HMDB) | |
Glutamine | Metabolite | HMDB00641 (HMDB) | |
HDL receptor | GeneProduct | ENSG00000073060 (Ensembl Human) | |
HMG CoA reductase | GeneProduct | ENSG00000113161 (Ensembl Human) | |
HMG CoA synthase | GeneProduct | ENSG00000112972 (Ensembl Human) | |
INSIG1 | GeneProduct | ENSG00000186480 (Ensembl Human) | |
INSIG2 | GeneProduct | ENSG00000125629 (Ensembl Human) | |
Insulin | Protein | P01308 (Uniprot/TrEMBL) | |
LDL receptor | GeneProduct | ENSG00000130164 (Ensembl Human) | |
LPIN1 | GeneProduct | ENSG00000134324 (Ensembl Human) | |
LXR | ENSG00000131408 (Ensembl Human) | ||
Lanosterol synthase | GeneProduct | ENSG00000160285 (Ensembl Human) | |
Lipoprotein lipase | GeneProduct | ENSG00000175445 (Ensembl Human) | |
NFY | GeneProduct | ENSG00000001167 (Ensembl Human) | |
Oxysterols | Metabolite | Oxysterols (Wikipedia) | |
PGC-1beta | GeneProduct | ENSG00000155846 (Ensembl Human) | |
PI3K | GeneProduct | ENSG00000121879 (Ensembl Human) | |
PPAR-gamma | GeneProduct | ENSG00000132170 (Ensembl Human) | |
PUFAs | Metabolite | Inhibition of SREBP1 processing | |
S1P | GeneProduct | ENSG00000140943 (Ensembl Human) | |
S2P | GeneProduct | ENSG00000012174 (Ensembl Human) | |
SAR1A | GeneProduct | ENSG00000079332 (Ensembl Human) | |
SAR1B | GeneProduct | ENSG00000152700 (Ensembl Human) | |
SCAP | GeneProduct | ENSG00000114650 (Ensembl Human) | |
SEC13 | GeneProduct | ENSG00000157020 (Ensembl Human) | |
SEC23A | GeneProduct | ENSG00000100934 (Ensembl Human) | |
SEC23B | GeneProduct | ENSG00000101310 (Ensembl Human) | |
SEC24A | GeneProduct | ENSG00000113615 (Ensembl Human) | |
SEC24B | GeneProduct | ENSG00000138802 (Ensembl Human) | |
SEC24C | GeneProduct | ENSG00000176986 (Ensembl Human) | |
SEC24D | GeneProduct | ENSG00000150961 (Ensembl Human) | |
SEC31A | GeneProduct | ENSG00000138674 (Ensembl Human) | |
SEC31B | GeneProduct | ENSG00000075826 (Ensembl Human) | |
SIRT1 | GeneProduct | ENSG00000096717 (Ensembl Human) | |
SP1 | GeneProduct | ENSG00000185591 (Ensembl Human) | |
SREBF2 | GeneProduct | ENSG00000198911 (Ensembl Human) | |
SREBP1a,-c | GeneProduct | ENSG00000072310 (Ensembl Human) | |
SREBP2 | GeneProduct | ENSG00000198911 (Ensembl Human) | |
TRC8 | GeneProduct | ||
UFAs | Metabolite | ||
YY1 | GeneProduct | ENSG00000100811 (Ensembl Human) | |
acetyl CoA synthetase | GeneProduct | ENSG00000154930 (Ensembl Human) | |
acetyl-CoA carboxylase | GeneProduct | ENSG00000132142 (Ensembl Human) | |
farnesyl diphosphate synthase | GeneProduct | ENSG00000160752 (Ensembl Human) | |
farnesyl-diphosphate farnesyltransferase | GeneProduct | ENSG00000079459 (Ensembl Human) | |
fatty acid synthase | GeneProduct | ENSG00000169710 (Ensembl Human) | |
glycerol-3-phosphate acyltransferase | GeneProduct | ENSG00000119927 (Ensembl Human) | |
importin beta | GeneProduct | ENSG00000108424 (Ensembl Human) | |
isopentenyl-diphosphate isomerase | GeneProduct | ENSG00000067064 (Ensembl Human) | |
lanosterol demethylase | GeneProduct | ENSG00000001630 (Ensembl Human) | |
mTOR complex 1 | GeneProduct | ENSG00000198793 (Ensembl Human) | |
malate dehydrogenase | GeneProduct | ENSG00000146701 (Ensembl Human) | |
mevalonate (diphospho) decarboxylase | GeneProduct | ENSG00000167508 (Ensembl Human) | |
miRNA33a | |||
miRNA33b | Rna | ||
nSREBP | GeneProduct | ||
nSREBP1a,-c | GeneProduct | ||
nSREBP2 | GeneProduct | ||
squalene epoxidase | GeneProduct | ENSG00000104549 (Ensembl Human) | |
stearoyl-CoA desaturase | GeneProduct | ENSG00000099194 (Ensembl Human) |
Annotated Interactions
No annotated interactions