{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:02:19Z","timestamp":1761742939665,"version":"3.44.0"},"reference-count":38,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical and Biophysical Research Communications"],"published-print":{"date-parts":[[2007,5]]},"DOI":"10.1016\/j.bbrc.2007.03.036","type":"journal-article","created":{"date-parts":[[2007,3,14]],"date-time":"2007-03-14T07:05:55Z","timestamp":1173855955000},"page":"693-698","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["N-terminal hamartin-binding and C-terminal GAP domain of tuberin can separate in vivo"],"prefix":"10.1016","volume":"356","author":[{"given":"Shuji","family":"Momose","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norihiro","family":"Tada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Itoyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Okio","family":"Hino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"year":"1999","series-title":"Tuberous Sclerosis Complex","author":"Gomez","key":"10.1016\/j.bbrc.2007.03.036_bib1"},{"key":"10.1016\/j.bbrc.2007.03.036_bib2","doi-asserted-by":"crossref","unstructured":"The European Chromosome 16 Tuberous Sclerosis Consortium, Identification and characterization of the tuberous sclerosis gene on chromosome 16, Cell 75 (1993) 1305\u20131315.","DOI":"10.1016\/0092-8674(93)90618-Z"},{"key":"10.1016\/j.bbrc.2007.03.036_bib3","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1126\/science.277.5327.805","article-title":"Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34","volume":"277","author":"van Slegtenhorst","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.bbrc.2007.03.036_bib4","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1093\/hmg\/7.6.1053","article-title":"Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products","volume":"7","author":"van Slegtenhorst","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.bbrc.2007.03.036_bib5","first-page":"4766","article-title":"Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles","volume":"58","author":"Plank","year":"1998","journal-title":"Cancer Res."},{"key":"10.1016\/j.bbrc.2007.03.036_bib6","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0092-8674(01)00332-4","article-title":"The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation","volume":"105","author":"Tapon","year":"2001","journal-title":"Cell"},{"key":"10.1016\/j.bbrc.2007.03.036_bib7","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1101\/gad.901101","article-title":"TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth","volume":"15","author":"Gao","year":"2001","journal-title":"Genes Dev."},{"key":"10.1016\/j.bbrc.2007.03.036_bib8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0092-8674(01)00333-6","article-title":"Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size","volume":"105","author":"Potter","year":"2001","journal-title":"Cell"},{"key":"10.1016\/j.bbrc.2007.03.036_bib9","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/S1097-2765(03)00220-X","article-title":"Insulin activation of Rheb, a mediator of mTOR\/S6K\/4E-BP signaling, is inhibited by TSC1 and 2","volume":"11","author":"Garami","year":"2003","journal-title":"Mol. Cell"},{"key":"10.1016\/j.bbrc.2007.03.036_bib10","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1101\/gad.1110003","article-title":"Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling","volume":"17","author":"Inoki","year":"2003","journal-title":"Genes Dev."},{"key":"10.1016\/j.bbrc.2007.03.036_bib11","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/S0960-9822(03)00506-2","article-title":"Tuberous sclerosis complex gene products, tuberin and hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb","volume":"13","author":"Tee","year":"2003","journal-title":"Curr. Biol."},{"key":"10.1016\/j.bbrc.2007.03.036_bib12","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/ncb999","article-title":"Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins","volume":"5","author":"Zhang","year":"2003","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.bbrc.2007.03.036_bib13","doi-asserted-by":"crossref","first-page":"35364","DOI":"10.1074\/jbc.M205838200","article-title":"Phosphatidylinositol 3-kinase\/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin","volume":"277","author":"Dan","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbrc.2007.03.036_bib14","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ncb839","article-title":"TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling","volume":"4","author":"Inoki","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.bbrc.2007.03.036_bib15","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S1097-2765(02)00568-3","article-title":"Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase\/akt pathway","volume":"10","author":"Manning","year":"2002","journal-title":"Mol. Cell"},{"key":"10.1016\/j.bbrc.2007.03.036_bib16","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/ncb840","article-title":"Akt regulates growth by directly phosphorylating Tsc2","volume":"4","author":"Potter","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.bbrc.2007.03.036_bib17","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1083\/jcb.200403069","article-title":"The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins","volume":"166","author":"Harrington","year":"2004","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.bbrc.2007.03.036_bib18","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.cub.2004.08.026","article-title":"Inappropriate activation of the TSC\/Rheb\/mTOR\/S6K cassette induces IRS1\/2 depletion, insulin resistance, and cell survival deficiencies","volume":"14","author":"Shah","year":"2004","journal-title":"Curr. Biol."},{"key":"10.1016\/j.bbrc.2007.03.036_bib19","first-page":"99","article-title":"Hereditary renal adenomas and adenocarcinomas in rats","volume":"4","author":"Eker","year":"1981","journal-title":"Diagn. Histopathol."},{"key":"10.1016\/j.bbrc.2007.03.036_bib20","doi-asserted-by":"crossref","first-page":"11413","DOI":"10.1073\/pnas.91.24.11413","article-title":"Predisposition to renal carcinoma in the Eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2) gene","volume":"91","author":"Yeung","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bbrc.2007.03.036_bib21","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ng0195-70","article-title":"A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer","volume":"9","author":"Kobayashi","year":"1995","journal-title":"Nat. Genet."},{"key":"10.1016\/j.bbrc.2007.03.036_bib22","first-page":"2633","article-title":"Allelic loss at the predisposing gene locus in spontaneous and chemically induced renal cell carcinomas in the Eker rat","volume":"54","author":"Kubo","year":"1994","journal-title":"Cancer Res."},{"key":"10.1016\/j.bbrc.2007.03.036_bib23","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1111\/j.1349-7006.1995.tb03092.x","article-title":"Allelic loss at the tuberous sclerosis (Tsc2) gene locus in spontaneous uterine leiomyosarcomas and pituitary adenomas in the Eker rat model","volume":"86","author":"Kubo","year":"1995","journal-title":"Jpn. J. Cancer Res."},{"key":"10.1016\/j.bbrc.2007.03.036_bib24","doi-asserted-by":"crossref","first-page":"3990","DOI":"10.1073\/pnas.94.8.3990","article-title":"Transgenic rescue from embryonic lethality and renal carcinogenesis in the Eker rat model by introduction of a wild-type Tsc2 gene","volume":"94","author":"Kobayashi","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bbrc.2007.03.036_bib25","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1093\/hmg\/11.24.2997","article-title":"Identification of the coding sequences responsible for Tsc2-mediated tumor suppression using a transgenic rat system","volume":"11","author":"Momose","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.bbrc.2007.03.036_bib26","first-page":"957","article-title":"Specific induction of hepatocellular adenomas by transplacental administration of ENU in the tsc2 gene mutant (Eker) rat","volume":"13","author":"Fukuda","year":"1998","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.bbrc.2007.03.036_bib27","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1038\/labinvest.3780143","article-title":"Distribution of Tsc1 protein detected by immunohistochemistry in various normal rat tissues and the renal carcinomas of Eker rat: detection of limited colocalization with Tsc1 and Tsc2 gene products in vivo","volume":"80","author":"Fukuda","year":"2000","journal-title":"Lab. Invest."},{"key":"10.1016\/j.bbrc.2007.03.036_bib28","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1073\/pnas.90.1.327","article-title":"Spontaneous and radiation-induced renal tumors in the Eker rat model of dominantly inherited cancer","volume":"90","author":"Hino","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bbrc.2007.03.036_bib29","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1093\/hmg\/5.1.131","article-title":"Comparative analysis and genomic structure of the tuberous sclerosis 2 (TSC2) gene in human and pufferfish","volume":"5","author":"Maheshwar","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.bbrc.2007.03.036_bib30","doi-asserted-by":"crossref","first-page":"35647","DOI":"10.1074\/jbc.274.50.35647","article-title":"Characterization of the cytosolic tuberin\u2013amartin complex. Tuberin is a cytosolic chaperone for hamartin","volume":"274","author":"Nellist","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbrc.2007.03.036_bib31","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1172\/JCI200317222","article-title":"Loss of Tsc1\/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR","volume":"112","author":"Zhang","year":"2003","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bbrc.2007.03.036_bib32","first-page":"5645","article-title":"Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors","volume":"62","author":"Kenerson","year":"2002","journal-title":"Cancer Res."},{"key":"10.1016\/j.bbrc.2007.03.036_bib33","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/hmg\/11.5.525","article-title":"A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells","volume":"11","author":"Kwiatkowski","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.bbrc.2007.03.036_bib34","doi-asserted-by":"crossref","first-page":"13571","DOI":"10.1073\/pnas.202476899","article-title":"Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling","volume":"99","author":"Tee","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bbrc.2007.03.036_bib35","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/ncb847","article-title":"Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling","volume":"4","author":"Gao","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.bbrc.2007.03.036_bib36","doi-asserted-by":"crossref","first-page":"7965","DOI":"10.1128\/MCB.24.18.7965-7975.2004","article-title":"Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity","volume":"24","author":"Li","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.bbrc.2007.03.036_bib37","doi-asserted-by":"crossref","first-page":"29930","DOI":"10.1074\/jbc.M402591200","article-title":"Regulation of B-Raf kinase activity by tuberin and Rheb is mammalian target of rapamycin (mTOR)-independent","volume":"279","author":"Karbowniczek","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbrc.2007.03.036_bib38","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cell.2005.02.031","article-title":"Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis","volume":"121","author":"Ma","year":"2005","journal-title":"Cell"}],"container-title":["Biochemical and Biophysical Research Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006291X07004949?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006291X07004949?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T10:32:19Z","timestamp":1757759539000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006291X07004949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,5]]}},"alternative-id":["S0006291X07004949"],"URL":"https:\/\/doi.org\/10.1016\/j.bbrc.2007.03.036","relation":{},"ISSN":["0006-291X"],"issn-type":[{"type":"print","value":"0006-291X"}],"subject":[],"published":{"date-parts":[[2007,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"N-terminal hamartin-binding and C-terminal GAP domain of tuberin can separate in vivo","name":"articletitle","label":"Article Title"},{"value":"Biochemical and Biophysical Research Communications","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbrc.2007.03.036","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2007 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}