{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:40:22Z","timestamp":1791200422965,"version":"4.2.0"},"reference-count":47,"publisher":"Cold Spring Harbor Laboratory","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[2001,6,1]]},"abstract":"<jats:p>Tuberous sclerosis is a human disease caused by mutations in the<jats:italic>TSC1<\/jats:italic> or the <jats:italic>TSC2<\/jats:italic> tumor suppressor gene. Previous studies of a <jats:italic>Drosophila TSC2<\/jats:italic> homolog suggested a role for the <jats:italic>TSC<\/jats:italic> genes in maintaining DNA content, with loss of<jats:italic>TSC2<\/jats:italic> leading to polyploidy and increased cell size. We have isolated mutations in the <jats:italic>Drosophila<\/jats:italic> homolog of the<jats:italic>TSC1<\/jats:italic> gene. We show that TSC1 and TSC2 form a complex and function in a common pathway to control cellular growth. Unlike previous studies, our work shows that <jats:italic>TSC1<\/jats:italic><jats:sup>\u2013<\/jats:sup> or<jats:italic>TSC2<\/jats:italic><jats:sup>\u2013<\/jats:sup> cells are diploid. We find that, strikingly, the heterozygosity of <jats:italic>TSC1<\/jats:italic> or <jats:italic>TSC2<\/jats:italic> is sufficient to rescue the lethality of loss-of-function insulin receptor mutants. Further genetic analyses suggest that the <jats:italic>TSC<\/jats:italic> genes act in a parallel pathway that converges on the insulin pathway downstream from<jats:italic>Akt<\/jats:italic>. Taken together, our studies identified the <jats:italic>TSC<\/jats:italic>tumor suppressors as novel negative regulators of insulin signaling.<\/jats:p>","DOI":"10.1101\/gad.901101","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T00:00:34Z","timestamp":1027728034000},"page":"1383-1392","source":"Crossref","is-referenced-by-count":376,"title":["<i>TSC1<\/i> and <i>TSC2<\/i> tumor suppressors antagonize insulin signaling in cell growth"],"prefix":"10.1101","volume":"15","author":[{"given":"Xinsheng","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duojia","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2001,6,1]]},"reference":[{"key":"2021111507394567000_15.11.1383.1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.107.1.17"},{"key":"2021111507394567000_15.11.1383.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80799-0"},{"key":"2021111507394567000_15.11.1383.3","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1242\/dev.118.2.401","article-title":"Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.","volume":"118","author":"Brand","year":"1993","journal-title":"Development"},{"key":"2021111507394567000_15.11.1383.4","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90306-W"},{"key":"2021111507394567000_15.11.1383.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.8.4240"},{"key":"2021111507394567000_15.11.1383.6","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1002\/j.1460-2075.1994.tb06768.x","article-title":"Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings.","volume":"13","author":"Capdevila","year":"1994","journal-title":"EMBO J."},{"key":"2021111507394567000_15.11.1383.7","doi-asserted-by":"publisher","DOI":"10.1210\/en.137.3.846"},{"key":"2021111507394567000_15.11.1383.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80563-2"},{"key":"2021111507394567000_15.11.1383.9","first-page":"1291","article-title":"Nuclear function and size in cancer cells.","volume":"152","author":"Derenzini","year":"1998","journal-title":"Am. 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