Connecting mTORC1 signaling to SREBP-1 activation

Laplante, 2009, Sabatini DM. mTOR signaling at a glance., J Cell Sci, 122, 3589, 10.1242/jcs.051011

Zoncu, 2011, mTOR: from growth signal integration to cancer, diabetes and ageing., Nat Rev Mol Cell Biol, 12, 21, 10.1038/nrm3025

Manning, 2007, AKTPKB signaling: navigating downstream., Cell, 129, 1261, 10.1016/j.cell.2007.06.009

Sancak, 2007, PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase., Mol Cell, 25, 903, 10.1016/j.molcel.2007.03.003

Vander Haar, 2007, Insulin signalling to mTOR mediated by the AktPKB substrate PRAS40., Nat Cell Biol, 9, 316, 10.1038/ncb1547

Wang, 2007, PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding., J Biol Chem, 282, 20036, 10.1074/jbc.M702376200

Thedieck, 2007, PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis., PLoS ONE, 2, e1217, 10.1371/journal.pone.0001217

Inoki, 2002, TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling., Nat Cell Biol, 4, 648, 10.1038/ncb839

Manning, 2002, Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinaseakt pathway., Mol Cell, 10, 151, 10.1016/S1097-2765(02)00568-3

Hara, 1998, Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism., J Biol Chem, 273, 14484, 10.1074/jbc.273.23.14484

Blommaart, 1995, Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes., J Biol Chem, 270, 2320, 10.1074/jbc.270.5.2320

Sancak, 2010, Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids., Cell, 141, 290, 10.1016/j.cell.2010.02.024

Sancak, 2009, Rag proteins regulate amino-acid-induced mTORC1 signalling., Biochem Soc Trans, 37, 289, 10.1042/BST0370289

Zoncu, 2011, mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H-ATPase., Science, 334, 678, 10.1126/science.1207056

Ma, 2009, Molecular mechanisms of mTOR-mediated translational control., Nat Rev Mol Cell Biol, 10, 307, 10.1038/nrm2672

Efeyan, 2010, mTOR and cancer: many loops in one pathway., Curr Opin Cell Biol, 22, 169, 10.1016/j.ceb.2009.10.007

Tzatsos, 2006, Nutrients suppress phosphatidylinositol 3-kinaseAkt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation., Mol Cell Biol, 26, 63, 10.1128/MCB.26.1.63-76.2006

Tzatsos, 2009, Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636639 by mTOR., J Biol Chem, 284, 22525, 10.1074/jbc.M109.027748

Harrington, 2004, The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins., J Cell Biol, 166, 213, 10.1083/jcb.200403069

Shah, 2006, Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis., Mol Cell Biol, 26, 6425, 10.1128/MCB.01254-05

Um, 2004, Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity., Nature, 431, 200, 10.1038/nature02866

Hsu, 2011, The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling., Science, 332, 1317, 10.1126/science.1199498

Yu, 2011, Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling., Science, 332, 1322, 10.1126/science.1199484

Ono, 2003, Hepatic Akt activation induces marked hypoglycemia, hepatomegaly, and hypertriglyceridemia with sterol regulatory element binding protein involvement., Diabetes, 52, 2905, 10.2337/diabetes.52.12.2905

Stiles, 2004, Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity corrected., Proc Natl Acad Sci U S A, 101, 2082, 10.1073/pnas.0308617100

Horie, 2004, Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas., J Clin Invest, 113, 1774, 10.1172/JCI20513

He, 2010, The critical role of AKT2 in hepatic steatosis induced by PTEN loss., Am J Pathol, 176, 2302, 10.2353/ajpath.2010.090931

Leavens, 2009, Akt2 is required for hepatic lipid accumulation in models of insulin resistance., Cell Metab, 10, 405, 10.1016/j.cmet.2009.10.004

Krycer, 2010, The Akt-SREBP nexus: cell signaling meets lipid metabolism., Trends Endocrinol Metab, 21, 268, 10.1016/j.tem.2010.01.001

Horton, 2002, SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver., J Clin Invest, 109, 1125, 10.1172/JCI0215593

Ferre, 2010, Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c., Diabetes Obes Metab, 12, 83, 10.1111/j.1463-1326.2010.01275.x

Yecies, 2011, Akt Stimulates Hepatic SREBP1c and Lipogenesis through Parallel mTORC1-Dependent and Independent Pathways., Cell Metab, 14, 21, 10.1016/j.cmet.2011.06.002

Yabe, 2003, Liver-specific mRNA for Insig-2 down-regulated by insulin: implications for fatty acid synthesis., Proc Natl Acad Sci U S A, 100, 3155, 10.1073/pnas.0130116100

Yellaturu, 2009, 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, 284, 31726, 10.1074/jbc.M109.050914

Yellaturu, 2009, Insulin enhances posttranslational processing of nascent SREBP-1c by promoting its phosphorylation and association with COPII vesicles., J Biol Chem, 284, 7518, 10.1074/jbc.M805746200

Sundqvist, 2005, Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7)., Cell Metab, 1, 379, 10.1016/j.cmet.2005.04.010

Li, 2010, Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis., Proc Natl Acad Sci U S A, 107, 3441, 10.1073/pnas.0914798107

Duvel, 2010, Activation of a metabolic gene regulatory network downstream of mTOR complex 1., Mol Cell, 39, 171, 10.1016/j.molcel.2010.06.022

Porstmann, 2008, SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth., Cell Metab, 8, 224, 10.1016/j.cmet.2008.07.007

Peterson, 2011, mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway., Cell, 146, 408, 10.1016/j.cell.2011.06.034

Li, 2011, Role of S6K1 in regulation of SREBP1c expression in the liver., Biochem Biophys Res Commun, 412, 197, 10.1016/j.bbrc.2011.07.038

Mauvoisin, 2007, Role of the PI3-kinasemTor pathway in the regulation of the stearoyl CoA desaturase (SCD1) gene expression by insulin in liver., J Cell Commun Signal, 1, 113, 10.1007/s12079-007-0011-1

Peng, 2002, The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation., Mol Cell Biol, 22, 5575, 10.1128/MCB.22.15.5575-5584.2002

Brown, 2007, The mammalian target of rapamycin regulates lipid metabolism in primary cultures of rat hepatocytes., Metabolism, 56, 1500, 10.1016/j.metabol.2007.06.016

Horton, 1998, Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice., Proc Natl Acad Sci U S A, 95, 5987, 10.1073/pnas.95.11.5987

Shimomura, 1999, Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes., Proc Natl Acad Sci U S A, 96, 13656, 10.1073/pnas.96.24.13656

Foretz, 1999, ADD1SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose., Mol Cell Biol, 19, 3760, 10.1128/MCB.19.5.3760

Pearce, 2010, Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1)., Biochem J, 431, 245, 10.1042/BJ20101024

Chen, 2004, 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, 101, 11245, 10.1073/pnas.0404297101

Repa, 2000, Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta., Genes Dev, 14, 2819, 10.1101/gad.844900

Hwahng, 2009, Role of adenosine monophosphate-activated protein kinase-p70 ribosomal S6 kinase-1 pathway in repression of liver X receptor-alpha-dependent lipogenic gene induction and hepatic steatosis by a novel class of dithiolethiones., Hepatology, 49, 1913, 10.1002/hep.22887

Amemiya-Kudo, 2000, Promoter analysis of the mouse sterol regulatory element-binding protein-1c gene., J Biol Chem, 275, 31078, 10.1074/jbc.M005353200

Ozcan, 2008, Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis., Mol Cell, 29, 541, 10.1016/j.molcel.2007.12.023

Kammoun, 2009, GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice., J Clin Invest, 119, 1201, 10.1172/JCI37007

Werstuck, 2001, Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways., J Clin Invest, 107, 1263, 10.1172/JCI11596

Caldwell, 2004, Obesity and hepatocellular carcinoma., Gastroenterology, 127, S97, 10.1053/j.gastro.2004.09.021

Donnelly, 2005, Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease., J Clin Invest, 115, 1343, 10.1172/JCI23621

Khamzina, 2005, Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance., Endocrinology, 146, 1473, 10.1210/en.2004-0921

Tremblay, 2007, Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance., Proc Natl Acad Sci U S A, 104, 14056, 10.1073/pnas.0706517104

Shigeyama, 2008, Biphasic response of pancreatic beta-cell mass to ablation of tuberous sclerosis complex 2 in mice., Mol Cell Biol, 28, 2971, 10.1128/MCB.01695-07

Kenerson, 2011, Tuberous sclerosis complex-1 deficiency attenuates diet-induced hepatic lipid accumulation., PLoS One, 6, e18075, 10.1371/journal.pone.0018075

Sengupta, 2010, mTORC1 controls fasting-induced ketogenesis and its modulation by ageing., Nature, 468, 1100, 10.1038/nature09584

Takaishi, 2004, Hepatic insig-1 or -2 overexpression reduces lipogenesis in obese Zucker diabetic fatty rats and in fastedrefed normal rats., Proc Natl Acad Sci U S A, 101, 7106, 10.1073/pnas.0401715101

Kim, 2010, Sterol regulatory element-binding protein (SREBP)-1-mediated lipogenesis is involved in cell senescence., J Biol Chem, 285, 29069, 10.1074/jbc.M110.120386

Shimomura, 1999, Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus., J Biol Chem, 274, 30028, 10.1074/jbc.274.42.30028

Li, 2008, Molecular mechanism of age-specific hepatic lipid accumulation in PPARalpha (-):LDLR (-) mice, an obese mouse model., Lipids, 43, 301, 10.1007/s11745-008-3161-x

Elam, 2010, Dysregulation of sterol regulatory element binding protein-1c in livers of morbidly obese women is associated with altered suppressor of cytokine signaling-3 and signal transducer and activator of transcription-1 signaling., Metabolism, 59, 587, 10.1016/j.metabol.2009.09.001