{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:34:00Z","timestamp":1791333240893,"version":"4.3.1"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"16","license":[{"start":{"date-parts":[[2011,7,29]],"date-time":"2011-07-29T00:00:00Z","timestamp":1311897600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2011,7,29]],"date-time":"2011-07-29T00:00:00Z","timestamp":1311897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO J"],"published-print":{"date-parts":[[2011,8,17]]},"DOI":"10.1038\/emboj.2011.257","type":"journal-article","created":{"date-parts":[[2011,7,29]],"date-time":"2011-07-29T10:08:50Z","timestamp":1311934130000},"page":"3242-3258","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":440,"title":["Regulation of TFEB and V\u2010ATPases by mTORC1"],"prefix":"10.1038","volume":"30","author":[{"given":"Samuel","family":"Pe\u00f1a\u2010Llopis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Vega\u2010Rubin\u2010de\u2010Celis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob C","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C","family":"Wolff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tram Anh T","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian\u2010Jin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Corey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Brugarolas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,7,29]]},"reference":[{"key":"BFEMBJ2011257_CR1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1517\/14728222.12.2.209","volume":"12","author":"RT Abraham","year":"2008","unstructured":"Abraham RT, Eng CH (2008) Mammalian target of rapamycin as a therapeutic target in oncology. Expert Opin Ther Targets 12: 209\u2013222","journal-title":"Expert Opin Ther Targets"},{"key":"BFEMBJ2011257_CR2","doi-asserted-by":"crossref","first-page":"E592","DOI":"10.1152\/ajpendo.90645.2008","volume":"296","author":"J Avruch","year":"2009","unstructured":"Avruch J, Long X, Ortiz\u2010Vega S, Rapley J, Papageorgiou A, Dai N (2009) Amino acid regulation of TOR complex 1. Am J Physiol Endocrinol Metab 296: E592\u2013E602","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"BFEMBJ2011257_CR3","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1242\/jeb.02014","volume":"209","author":"KW Beyenbach","year":"2006","unstructured":"Beyenbach KW, Wieczorek H (2006) The V\u2010type H+ ATPase: molecular structure and function, physiological roles and regulation. J Exp Biol 209: 577\u2013589","journal-title":"J Exp Biol"},{"key":"BFEMBJ2011257_CR4","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1074\/jbc.M109756200","volume":"277","author":"BJ Bowman","year":"2002","unstructured":"Bowman BJ, Bowman EJ (2002) Mutations in subunit C of the vacuolar ATPase confer resistance to bafilomycin and identify a conserved antibiotic binding site. J Biol Chem 277: 3965\u20133972","journal-title":"J Biol Chem"},{"key":"BFEMBJ2011257_CR5","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1101\/gad.1256804","volume":"18","author":"J Brugarolas","year":"2004","unstructured":"Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin Jr WG (2004) Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1\/TSC2 tumor suppressor complex. Genes Dev 18: 2893\u20132904","journal-title":"Genes Dev"},{"key":"BFEMBJ2011257_CR6","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S1535-6108(03)00187-9","volume":"4","author":"JB Brugarolas","year":"2003","unstructured":"Brugarolas JB, Vazquez F, Reddy A, Sellers WR, Kaelin Jr WG (2003) TSC2 regulates VEGF through mTOR\u2010dependent and \u2010independent pathways. Cancer Cell 4: 147\u2013158","journal-title":"Cancer Cell"},{"key":"BFEMBJ2011257_CR7","doi-asserted-by":"crossref","first-page":"32493","DOI":"10.1074\/jbc.C300226200","volume":"278","author":"AF Castro","year":"2003","unstructured":"Castro AF, Rebhun JF, Clark GG, Quilliam LA (2003) Rheb binds TSC2 and promotes S6 kinase activation in a rapamycin\u2010 and farnesylation\u2010dependent manner. J Biol Chem 278: 32493\u201332496","journal-title":"J Biol Chem"},{"key":"BFEMBJ2011257_CR8","doi-asserted-by":"crossref","first-page":"3955","DOI":"10.1128\/MCB.26.10.3955-3965.2006","volume":"26","author":"E Connolly","year":"2006","unstructured":"Connolly E, Braunstein S, Formenti S, Schneider RJ (2006) Hypoxia inhibits protein synthesis through a 4E\u2010BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells. Mol Cell Biol 26: 3955\u20133965","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2011257_CR9","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1101\/gad.1199104","volume":"18","author":"MN Corradetti","year":"2004","unstructured":"Corradetti MN, Inoki K, Bardeesy N, DePinho RA, Guan KL (2004) Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz\u2010Jeghers syndrome. Genes Dev 18: 1533\u20131538","journal-title":"Genes Dev"},{"key":"BFEMBJ2011257_CR10","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nature06322","volume":"450","author":"JT Cunningham","year":"2007","unstructured":"Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P (2007) mTOR controls mitochondrial oxidative function through a YY1\u2010PGC\u20101alpha transcriptional complex. Nature 450: 736\u2013740","journal-title":"Nature"},{"key":"BFEMBJ2011257_CR11","doi-asserted-by":"crossref","first-page":"35364","DOI":"10.1074\/jbc.M205838200","volume":"277","author":"HC Dan","year":"2002","unstructured":"Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ (2002) Phosphatidylinositol 3\u2010kinase\/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin. J Biol Chem 277: 35364\u201335370","journal-title":"J Biol Chem"},{"key":"BFEMBJ2011257_CR12","doi-asserted-by":"crossref","first-page":"6051","DOI":"10.1073\/pnas.0931430100","volume":"100","author":"IJ Davis","year":"2003","unstructured":"Davis IJ, Hsi BL, Arroyo JD, Vargas SO, Yeh YA, Motyckova G, Valencia P, Perez\u2010Atayde AR, Argani P, Ladanyi M, Fletcher JA, Fisher DE (2003) Cloning of an alpha\u2010TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation. Proc Natl Acad Sci USA 100: 6051\u20136056","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2011257_CR13","doi-asserted-by":"crossref","first-page":"10762","DOI":"10.1073\/pnas.0805139105","volume":"105","author":"N Dephoure","year":"2008","unstructured":"Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci USA 105: 10762\u201310767","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2011257_CR14","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1101\/gad.1617608","volume":"22","author":"MP DeYoung","year":"2008","unstructured":"DeYoung MP, Horak P, Sofer A, Sgroi D, Ellisen LW (2008) Hypoxia regulates TSC1\/2\u2010mTOR signaling and tumor suppression through REDD1\u2010mediated 14\u20103\u20103 shuttling. Genes Dev 22: 239\u2013251","journal-title":"Genes Dev"},{"key":"BFEMBJ2011257_CR15","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.molcel.2010.06.022","volume":"39","author":"K Duvel","year":"2010","unstructured":"Duvel 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 (2010) Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell 39: 171\u2013183","journal-title":"Mol Cell"},{"key":"BFEMBJ2011257_CR16","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1016\/S0140-6736(03)13044-9","volume":"361","author":"N El\u2010Hashemite","year":"2003","unstructured":"El\u2010Hashemite N, Zhang H, Henske EP, Kwiatkowski DJ (2003) Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma. Lancet 361: 1348\u20131349","journal-title":"Lancet"},{"key":"BFEMBJ2011257_CR17","doi-asserted-by":"crossref","first-page":"3151","DOI":"10.1038\/sj.onc.1207542","volume":"23","author":"DC Fingar","year":"2004","unstructured":"Fingar DC, Blenis J (2004) Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 23: 3151\u20133171","journal-title":"Oncogene"},{"key":"BFEMBJ2011257_CR18","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1091\/mbc.e09-09-0756","volume":"21","author":"RJ Flinn","year":"2010","unstructured":"Flinn RJ, Yan Y, Goswami S, Parker PJ, Backer JM (2010) The late endosome is essential for mTORC1 signaling. Mol Biol Cell 21: 833\u2013841","journal-title":"Mol Biol Cell"},{"key":"BFEMBJ2011257_CR19","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nrm2272","volume":"8","author":"M Forgac","year":"2007","unstructured":"Forgac M (2007) Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology. Nat Rev Mol Cell Biol 8: 917\u2013929","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFEMBJ2011257_CR20","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/S1097-2765(03)00220-X","volume":"11","author":"A Garami","year":"2003","unstructured":"Garami A, Zwartkruis FJ, Nobukuni T, Joaquin M, Roccio M, Stocker H, Kozma SC, Hafen E, Bos JL, Thomas G (2003) Insulin activation of Rheb, a mediator of mTOR\/S6K\/4E\u2010BP signaling, is inhibited by TSC1 and 2. Mol Cell 11: 1457\u20131466","journal-title":"Mol Cell"},{"key":"BFEMBJ2011257_CR21","unstructured":"Guyton AC, Hall JE (1996) Texbook of Medical Physiology, 9th edn, Philadelphia, PA: WB Saunders Company"},{"key":"BFEMBJ2011257_CR22","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2008.03.003","volume":"30","author":"DM Gwinn","year":"2008","unstructured":"Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30: 214\u2013226","journal-title":"Mol Cell"},{"key":"BFEMBJ2011257_CR23","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0092-8674(02)00833-4","volume":"110","author":"K Hara","year":"2002","unstructured":"Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K (2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110: 177\u2013189","journal-title":"Cell"},{"key":"BFEMBJ2011257_CR24","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","volume":"43","author":"C He","year":"2009","unstructured":"He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43: 67\u201393","journal-title":"Annu Rev Genet"},{"key":"BFEMBJ2011257_CR25","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1083\/jcb.200511140","volume":"173","author":"KM Hennig","year":"2006","unstructured":"Hennig KM, Colombani J, Neufeld TP (2006) TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth. J Cell Biol 173: 963\u2013974","journal-title":"J Cell Biol"},{"key":"BFEMBJ2011257_CR26","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1056\/NEJMoa066838","volume":"356","author":"G Hudes","year":"2007","unstructured":"Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt\u2010Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ (2007) Temsirolimus, interferon alfa, or both for advanced renal\u2010cell carcinoma. N Engl J Med 356: 2271\u20132281","journal-title":"N Engl J Med"},{"key":"BFEMBJ2011257_CR27","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1101\/gad.1110003","volume":"17","author":"K Inoki","year":"2003","unstructured":"Inoki K, Li Y, Xu T, Guan KL (2003a) Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 17: 1829\u20131834","journal-title":"Genes Dev"},{"key":"BFEMBJ2011257_CR28","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ncb839","volume":"4","author":"K Inoki","year":"2002","unstructured":"Inoki K, Li Y, Zhu T, Wu J, Guan KL (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4: 648\u2013657","journal-title":"Nat Cell Biol"},{"key":"BFEMBJ2011257_CR29","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(03)00929-2","volume":"115","author":"K Inoki","year":"2003","unstructured":"Inoki K, Zhu T, Guan KL (2003b) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115: 577\u2013590","journal-title":"Cell"},{"key":"BFEMBJ2011257_CR30","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/ncb1183","volume":"6","author":"E Jacinto","year":"2004","unstructured":"Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, Hall A, Hall MN (2004) Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6: 1122\u20131128","journal-title":"Nat Cell Biol"},{"key":"BFEMBJ2011257_CR31","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1083\/jcb.jcb.200206108","volume":"159","author":"A Jaeschke","year":"2002","unstructured":"Jaeschke A, Hartkamp J, Saitoh M, Roworth W, Nobukuni T, Hodges A, Sampson J, Thomas G, Lamb R (2002) Tuberous sclerosis complex tumor suppressor\u2010mediated S6 kinase inhibition by phosphatidylinositide\u20103\u2010OH kinase is mTOR independent. J Cell Biol 159: 217\u2013224","journal-title":"J Cell Biol"},{"key":"BFEMBJ2011257_CR32","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nrc2502","volume":"8","author":"Jr WG Kaelin","year":"2008","unstructured":"Kaelin Jr WG (2008) The von Hippel\u2010Lindau tumour suppressor protein: O2 sensing and cancer. Nat Rev Cancer 8: 865\u2013873","journal-title":"Nat Rev Cancer"},{"key":"BFEMBJ2011257_CR33","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1158\/0008-5472.CAN-05-3375","volume":"66","author":"F Kaper","year":"2006","unstructured":"Kaper F, Dornhoefer N, Giaccia AJ (2006) Mutations in the PI3K\/PTEN\/TSC2 pathway contribute to mammalian target of rapamycin activity and increased translation under hypoxic conditions. Cancer Res 66: 1561\u20131569","journal-title":"Cancer Res"},{"key":"BFEMBJ2011257_CR34","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.humpath.2007.01.028","volume":"38","author":"H Kenerson","year":"2007","unstructured":"Kenerson H, Folpe AL, Takayama TK, Yeung RS (2007) Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms. Hum Pathol 38: 1361\u20131371","journal-title":"Hum Pathol"},{"key":"BFEMBJ2011257_CR35","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0092-8674(02)00808-5","volume":"110","author":"DH Kim","year":"2002","unstructured":"Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument\u2010Bromage H, Tempst P, Sabatini DM (2002) mTOR interacts with raptor to form a nutrient\u2010sensitive complex that signals to the cell growth machinery. Cell 110: 163\u2013175","journal-title":"Cell"},{"key":"BFEMBJ2011257_CR36","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/ncb1753","volume":"10","author":"E Kim","year":"2008","unstructured":"Kim E, Goraksha\u2010Hicks P, Li L, Neufeld TP, Guan KL (2008) Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 10: 935\u2013945","journal-title":"Nat Cell Biol"},{"key":"BFEMBJ2011257_CR37","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/ncb2204","volume":"13","author":"VI Korolchuk","year":"2011","unstructured":"Korolchuk VI, Saiki S, Lichtenberg M, Siddiqi FH, Roberts EA, Imarisio S, Jahreiss L, Sarkar S, Futter M, Menzies FM, O'Kane CJ, Deretic V, Rubinsztein DC (2011) Lysosomal positioning coordinates cellular nutrient responses. Nat Cell Biol 13: 453\u2013460","journal-title":"Nat Cell Biol"},{"key":"BFEMBJ2011257_CR38","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.molcel.2010.09.023","volume":"40","author":"G Kroemer","year":"2010","unstructured":"Kroemer G, Marino G, Levine B (2010) Autophagy and the integrated stress response. Mol Cell 40: 280\u2013293","journal-title":"Mol Cell"},{"key":"BFEMBJ2011257_CR39","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1038\/onc.2010.587","volume":"30","author":"B Kucejova","year":"2011","unstructured":"Kucejova B, Sunny NE, Nguyen AD, Hallac R, Fu X, Pena\u2010Llopis S, Mason RP, Deberardinis RJ, Xie XJ, Debose\u2010Boyd R, Kodibagkar VD, Burgess SC, Brugarolas J (2011) Uncoupling hypoxia signaling from oxygen sensing in the liver results in hypoketotic hypoglycemic death. Oncogene 30: 2147\u20132160","journal-title":"Oncogene"},{"key":"BFEMBJ2011257_CR40","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1093\/hmg\/ddg178","volume":"12","author":"RP Kuiper","year":"2003","unstructured":"Kuiper RP, Schepens M, Thijssen J, van Asseldonk M, van den Berg E, Bridge J, Schuuring E, Schoenmakers EF, van Kessel AG (2003) Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)\u2010positive renal cell carcinomas due to promoter substitution. Hum Mol Genet 12: 1661\u20131669","journal-title":"Hum Mol Genet"},{"key":"BFEMBJ2011257_CR41","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/hmg\/11.5.525","volume":"11","author":"DJ Kwiatkowski","year":"2002","unstructured":"Kwiatkowski DJ, Zhang H, Bandura JL, Heiberger KM, Glogauer M, El\u2010Hashemite N, Onda H (2002) A mouse model of TSC1 reveals sex\u2010dependent lethality from liver hemangiomas, and up\u2010regulation of p70S6 kinase activity in Tsc1 null cells. Hum Mol Genet 11: 525\u2013534","journal-title":"Hum Mol Genet"},{"key":"BFEMBJ2011257_CR42","doi-asserted-by":"crossref","first-page":"19705","DOI":"10.1074\/jbc.C110.102483","volume":"285","author":"L Li","year":"2010","unstructured":"Li L, Kim E, Yuan H, Inoki K, Goraksha\u2010Hicks P, Schiesher RL, Neufeld TP, Guan KL (2010) Regulation of mTORC1 by the Rab and Arf GTPases. J Biol Chem 285: 19705\u201319709","journal-title":"J Biol Chem"},{"key":"BFEMBJ2011257_CR43","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.molcel.2006.01.010","volume":"21","author":"L Liu","year":"2006","unstructured":"Liu L, Cash TP, Jones RG, Keith B, Thompson CB, Simon MC (2006) Hypoxia\u2010induced energy stress regulates mRNA translation and cell growth. Mol Cell 21: 521\u2013531","journal-title":"Mol Cell"},{"key":"BFEMBJ2011257_CR44","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S1097-2765(02)00636-6","volume":"10","author":"R Loewith","year":"2002","unstructured":"Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, Oppliger W, Jenoe P, Hall MN (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10: 457\u2013468","journal-title":"Mol Cell"},{"key":"BFEMBJ2011257_CR45","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cell.2005.02.031","volume":"121","author":"L Ma","year":"2005","unstructured":"Ma L, Chen Z, Erdjument\u2010Bromage H, Tempst P, Pandolfi PP (2005) Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 121: 179\u2013193","journal-title":"Cell"},{"key":"BFEMBJ2011257_CR46","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nm1052","volume":"10","author":"PK Majumder","year":"2004","unstructured":"Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, Manola J, Brugarolas J, McDonnell TJ, Golub TR, Loda M, Lane HA, Sellers WR (2004) mTOR inhibition reverses Akt\u2010dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF\u20101\u2010dependent pathways. Nat Med 10: 594\u2013601","journal-title":"Nat Med"},{"key":"BFEMBJ2011257_CR47","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S1097-2765(02)00568-3","volume":"10","author":"BD Manning","year":"2002","unstructured":"Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC (2002) Identification of the tuberous sclerosis complex\u20102 tumor suppressor gene product tuberin as a target of the phosphoinositide 3\u2010kinase\/akt pathway. Mol Cell 10: 151\u2013162","journal-title":"Mol Cell"},{"key":"BFEMBJ2011257_CR48","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ceb.2008.03.015","volume":"20","author":"V Marshansky","year":"2008","unstructured":"Marshansky V, Futai M (2008) The V\u2010type H+\u2010ATPase in vesicular trafficking: targeting, regulation and function. Curr Opin Cell Biol 20: 415\u2013426","journal-title":"Curr Opin Cell Biol"},{"key":"BFEMBJ2011257_CR49","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/modpathol.2009.58","volume":"22","author":"G Martignoni","year":"2009","unstructured":"Martignoni G, Pea M, Gobbo S, Brunelli M, Bonetti F, Segala D, Pan CC, Netto G, Doglioni C, Hes O, Argani P, Chilosi M (2009) Cathepsin\u2010K immunoreactivity distinguishes MiTF\/TFE family renal translocation carcinomas from other renal carcinomas. Mod Pathol 22: 1016\u20131022","journal-title":"Mod Pathol"},{"key":"BFEMBJ2011257_CR50","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s00428-007-0509-1","volume":"452","author":"G Martignoni","year":"2008","unstructured":"Martignoni G, Pea M, Reghellin D, Zamboni G, Bonetti F (2008) PEComas: the past, the present and the future. Virchows Arch 452: 119\u2013132","journal-title":"Virchows Arch"},{"key":"BFEMBJ2011257_CR51","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrm2216","volume":"8","author":"S Mayor","year":"2007","unstructured":"Mayor S, Pagano RE (2007) Pathways of clathrin\u2010independent endocytosis. Nat Rev Mol Cell Biol 8: 603\u2013612","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFEMBJ2011257_CR52","doi-asserted-by":"crossref","first-page":"ra46","DOI":"10.1126\/scisignal.2000007","volume":"2","author":"V Mayya","year":"2009","unstructured":"Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK (2009) Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system\u2010wide modulation of protein\u2010protein interactions. Sci Signal 2: ra46","journal-title":"Sci Signal"},{"key":"BFEMBJ2011257_CR53","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0140-6736(08)61039-9","volume":"372","author":"RJ Motzer","year":"2008","unstructured":"Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double\u2010blind, randomised, placebo\u2010controlled phase III trial. Lancet 372: 449\u2013456","journal-title":"Lancet"},{"key":"BFEMBJ2011257_CR54","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1126\/science.1205407","volume":"332","author":"M Narita","year":"2011","unstructured":"Narita M, Young AR, Arakawa S, Samarajiwa SA, Nakashima T, Yoshida S, Hong S, Berry LS, Reichelt S, Ferreira M, Tavare S, Inoki K, Shimizu S (2011) Spatial coupling of mTOR and autophagy augments secretory phenotypes. Science 332: 966\u2013970","journal-title":"Science"},{"key":"BFEMBJ2011257_CR55","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1074\/jbc.M607275200","volume":"282","author":"SM Nemetski","year":"2007","unstructured":"Nemetski SM, Gardner LB (2007) Hypoxic regulation of Id\u20101 and activation of the unfolded protein response are aberrant in neuroblastoma. J Biol Chem 282: 240\u2013248","journal-title":"J Biol Chem"},{"key":"BFEMBJ2011257_CR56","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nature03571","volume":"436","author":"L Pelkmans","year":"2005","unstructured":"Pelkmans L, Fava E, Grabner H, Hannus M, Habermann B, Krausz E, Zerial M (2005) Genome\u2010wide analysis of human kinases in clathrin\u2010 and caveolae\/raft\u2010mediated endocytosis. Nature 436: 78\u201386","journal-title":"Nature"},{"key":"BFEMBJ2011257_CR57","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.cmet.2008.07.007","volume":"8","author":"T Porstmann","year":"2008","unstructured":"Porstmann T, Santos CR, Griffiths B, Cully M, Wu M, Leevers S, Griffiths JR, Chung YL, Schulze A (2008) SREBP activity is regulated by mTORC1 and contributes to Akt\u2010dependent cell growth. Cell Metab 8: 224\u2013236","journal-title":"Cell Metab"},{"key":"BFEMBJ2011257_CR58","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/ncb840","volume":"4","author":"CJ Potter","year":"2002","unstructured":"Potter CJ, Pedraza LG, Xu T (2002) Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol 4: 658\u2013665","journal-title":"Nat Cell Biol"},{"key":"BFEMBJ2011257_CR59","doi-asserted-by":"crossref","first-page":"38121","DOI":"10.1074\/jbc.M105408200","volume":"276","author":"B Razani","year":"2001","unstructured":"Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB, Macaluso F, Russell RG, Li M, Pestell RG, Di Vizio D, Hou Jr H, Kneitz B, Lagaud G, Christ GJ, Edelmann W, Lisanti MP (2001) Caveolin\u20101 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276: 38121\u201338138","journal-title":"J Biol Chem"},{"key":"BFEMBJ2011257_CR60","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/sj.onc.1209106","volume":"25","author":"M Roccio","year":"2006","unstructured":"Roccio M, Bos JL, Zwartkruis FJ (2006) Regulation of the small GTPase Rheb by amino acids. Oncogene 25: 657\u2013664","journal-title":"Oncogene"},{"key":"BFEMBJ2011257_CR61","doi-asserted-by":"crossref","first-page":"7826","DOI":"10.1073\/pnas.1013800108","volume":"108","author":"Y Rong","year":"2011","unstructured":"Rong Y, McPhee C, Deng S, Huang L, Chen L, Liu M, Tracy K, Baehreck EH, Yu L, Lenardo MJ (2011) Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation. Proc Natl Acad Sci USA 108: 7826\u20137831","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2011257_CR62","doi-asserted-by":"crossref","first-page":"13489","DOI":"10.1073\/pnas.0405659101","volume":"101","author":"PP Roux","year":"2004","unstructured":"Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J (2004) Tumor\u2010promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci USA 101: 13489\u201313494","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2011257_CR63","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.cell.2010.02.024","volume":"141","author":"Y Sancak","year":"2010","unstructured":"Sancak Y, Bar\u2010Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM (2010) Ragulator\u2010Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141: 290\u2013303","journal-title":"Cell"},{"key":"BFEMBJ2011257_CR64","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1126\/science.1157535","volume":"320","author":"Y Sancak","year":"2008","unstructured":"Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar\u2010Peled L, Sabatini DM (2008) The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320: 1496\u20131501","journal-title":"Science"},{"key":"BFEMBJ2011257_CR65","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.molcel.2007.03.003","volume":"25","author":"Y Sancak","year":"2007","unstructured":"Sancak Y, Thoreen CC, Peterson TR, Lindquist RA, Kang SA, Spooner E, Carr SA, Sabatini DM (2007) PRAS40 is an insulin\u2010regulated inhibitor of the mTORC1 protein kinase. Mol Cell 25: 903\u2013915","journal-title":"Mol Cell"},{"key":"BFEMBJ2011257_CR66","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.cub.2004.06.054","volume":"14","author":"DD Sarbassov","year":"2004","unstructured":"Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument\u2010Bromage H, Tempst P, Sabatini DM (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin\u2010insensitive and raptor\u2010independent pathway that regulates the cytoskeleton. Curr Biol 14: 1296\u20131302","journal-title":"Curr Biol"},{"key":"BFEMBJ2011257_CR67","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.1174447","volume":"325","author":"M Sardiello","year":"2009","unstructured":"Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, Di Malta C, Donaudy F, Embrione V, Polishchuk RS, Banfi S, Parenti G, Cattaneo E, Ballabio A (2009) A gene network regulating lysosomal biogenesis and function. Science 325: 473\u2013477","journal-title":"Science"},{"key":"BFEMBJ2011257_CR68","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.1204592","volume":"332","author":"C Settembre","year":"2011","unstructured":"Settembre C, Di Malta C, Polito VA, Arencibia MG, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P, Sardiello M, Rubinsztein DC, Ballabio A (2011) TFEB links autophagy to lysosomal biogenesis. Science 332: 1429\u20131433","journal-title":"Science"},{"key":"BFEMBJ2011257_CR69","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ccr.2004.06.007","volume":"6","author":"RJ Shaw","year":"2004","unstructured":"Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA, Cantley LC (2004) The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell 6: 91\u201399","journal-title":"Cancer Cell"},{"key":"BFEMBJ2011257_CR70","doi-asserted-by":"crossref","first-page":"18717","DOI":"10.1074\/jbc.M414499200","volume":"280","author":"EM Smith","year":"2005","unstructured":"Smith EM, Finn SG, Tee AR, Browne GJ, Proud CG (2005) The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses. J Biol Chem 280: 18717\u201318727","journal-title":"J Biol Chem"},{"key":"BFEMBJ2011257_CR71","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.cell.2009.01.042","volume":"136","author":"N Sonenberg","year":"2009","unstructured":"Sonenberg N, Hinnebusch AG (2009) Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136: 731\u2013745","journal-title":"Cell"},{"key":"BFEMBJ2011257_CR72","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/modpathol.2009.70","volume":"22","author":"JR Srigley","year":"2009","unstructured":"Srigley JR, Delahunt B (2009) Uncommon and recently described renal carcinomas. Mod Pathol 22(Suppl 2): S2\u2013S23","journal-title":"Mod Pathol"},{"key":"BFEMBJ2011257_CR73","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev.genet.38.072902.092717","volume":"38","author":"E Steingrimsson","year":"2004","unstructured":"Steingrimsson E, Copeland NG, Jenkins NA (2004) Melanocytes and the microphthalmia transcription factor network. Annu Rev Genet 38: 365\u2013411","journal-title":"Annu Rev Genet"},{"key":"BFEMBJ2011257_CR74","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/S0960-9822(03)00506-2","volume":"13","author":"AR Tee","year":"2003","unstructured":"Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J (2003) Tuberous sclerosis complex gene products, tuberin and hamartin, control mTOR signaling by acting as a GTPase\u2010activating protein complex toward Rheb. Curr Biol 13: 1259\u20131268","journal-title":"Curr Biol"},{"key":"BFEMBJ2011257_CR75","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1021\/bi902135e","volume":"49","author":"S Vega\u2010Rubin\u2010de\u2010Celis","year":"2010","unstructured":"Vega\u2010Rubin\u2010de\u2010Celis S, Abdallah Z, Kinch L, Grishin NV, Brugarolas J, Zhang X (2010) Structural analysis and functional implications of the negative mTORC1 regulator REDD1. Biochemistry 49: 2491\u20132501","journal-title":"Biochemistry"},{"key":"BFEMBJ2011257_CR76","doi-asserted-by":"crossref","first-page":"re12","DOI":"10.1126\/stke.3062005re12","volume":"2005","author":"RH Wenger","year":"2005","unstructured":"Wenger RH, Stiehl DP, Camenisch G (2005) Integration of oxygen signaling at the consensus HRE. Sci STKE 2005: re12","journal-title":"Sci STKE"},{"key":"BFEMBJ2011257_CR77","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1128\/MCB.01393-10","volume":"31","author":"NC Wolff","year":"2011","unstructured":"Wolff NC, Vega\u2010Rubin\u2010de\u2010Celis S, Xie XJ, Castrillon DH, Kabbani W, Brugarolas J (2011) Cell\u2010type\u2010dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1\/TSC2 and LKB1 in response to hypoxia. Mol Cell Biol 31: 1870\u20131884","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2011257_CR78","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","volume":"124","author":"S Wullschleger","year":"2006","unstructured":"Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124: 471\u2013484","journal-title":"Cell"},{"key":"BFEMBJ2011257_CR79","doi-asserted-by":"crossref","first-page":"4260","DOI":"10.1073\/pnas.0810067106","volume":"106","author":"X Xia","year":"2009","unstructured":"Xia X, Lemieux ME, Li W, Carroll JS, Brown M, Liu XS, Kung AL (2009) Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. Proc Natl Acad Sci USA 106: 4260\u20134265","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2011257_CR80","doi-asserted-by":"crossref","first-page":"6097","DOI":"10.1074\/jbc.272.10.6097","volume":"272","author":"GH Xiao","year":"1997","unstructured":"Xiao GH, Shoarinejad F, Jin F, Golemis EA, Yeung RS (1997) The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis. J Biol Chem 272: 6097\u20136100","journal-title":"J Biol Chem"},{"key":"BFEMBJ2011257_CR81","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nature09076","volume":"465","author":"L Yu","year":"2010","unstructured":"Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J, Mi N, Zhao Y, Liu Z, Wan F, Hailey DW, Oorschot V, Klumperman J, Baehrecke EH, Lenardo MJ (2010) Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465: 942\u2013946","journal-title":"Nature"},{"key":"BFEMBJ2011257_CR82","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1126\/science.1199484","volume":"332","author":"Y Yu","year":"2011","unstructured":"Yu Y, Yoon SO, Poulogiannis G, Yang Q, Ma XM, Villen J, Kubica N, Hoffman GR, Cantley LC, Gygi SP, Blenis J (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332: 1322\u20131326","journal-title":"Science"},{"key":"BFEMBJ2011257_CR83","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1172\/JCI200317222","volume":"112","author":"H Zhang","year":"2003","unstructured":"Zhang H, Cicchetti G, Onda H, Koon HB, Asrican K, Bajraszewski N, Vazquez F, Carpenter CL, Kwiatkowski DJ (2003a) Loss of Tsc1\/Tsc2 activates mTOR and disrupts PI3K\u2010Akt signaling through downregulation of PDGFR. J Clin Invest 112: 1223\u20131233","journal-title":"J Clin Invest"},{"key":"BFEMBJ2011257_CR84","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/ncb999","volume":"5","author":"Y Zhang","year":"2003","unstructured":"Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA, Pan D (2003b) Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat Cell Biol 5: 578\u2013581","journal-title":"Nat Cell Biol"}],"container-title":["The EMBO Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Femboj.2011.257","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/emboj.2011.257.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1038\/emboj.2011.257","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/emboj.2011.257.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:16:48Z","timestamp":1779236208000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1038\/emboj.2011.257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7,29]]},"references-count":84,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2011,8,17]]}},"alternative-id":["BFEMBJ2011257"],"URL":"https:\/\/doi.org\/10.1038\/emboj.2011.257","relation":{},"ISSN":["0261-4189","1460-2075"],"issn-type":[{"value":"0261-4189","type":"print"},{"value":"1460-2075","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,7,29]]},"assertion":[{"value":"21 December 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2011","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2011","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}