{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:40:14Z","timestamp":1792104014819,"version":"4.4.0"},"reference-count":23,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6125","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2013,3,15]]},"abstract":"<jats:title>Coordinating Metabolism<\/jats:title>\n          <jats:p>\n            Growth factors help to coordinate metabolism with growth in part by stimulating the activity of the protein kinase mTORC1 (mechanistic target of rapamycin complex 1).\n            <jats:bold>\n              Ben-Sahra\n              <jats:italic>et al.<\/jats:italic>\n            <\/jats:bold>\n            (p.\n            <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" issue=\"6125\" page=\"1323\" related-article-type=\"in-this-issue\" vol=\"339\" xlink:href=\"10.1126\/science.1228792\">1323<\/jats:related-article>\n            , published online 21 February) and\n            <jats:bold>\n              Robitaille\n              <jats:italic>et al.<\/jats:italic>\n            <\/jats:bold>\n            (p.\n            <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" issue=\"6125\" page=\"1320\" related-article-type=\"in-this-issue\" vol=\"339\" xlink:href=\"10.1126\/science.1228771\">1320<\/jats:related-article>\n            , published online 21 February) independently identified a key target of mTORC1\u2014carbamolyl-phosphate synthase 2, or CAD, the rate-limiting enzyme for de novo synthesis of pyrimidines. Metabolomic profiling and phosphoproteomic analyses of normal cells and cells lacking signaling by mTORC1 converged on CAD as a key point at which growth-promoting signals also ramp up production of nucleic acids.\n          <\/jats:p>","DOI":"10.1126\/science.1228792","type":"journal-article","created":{"date-parts":[[2013,2,22]],"date-time":"2013-02-22T05:05:15Z","timestamp":1361509515000},"page":"1323-1328","source":"Crossref","is-referenced-by-count":725,"title":["Stimulation of de Novo Pyrimidine Synthesis by Growth Signaling Through mTOR and S6K1"],"prefix":"10.1126","volume":"339","author":[{"given":"Issam","family":"Ben-Sahra","sequence":"first","affiliation":[{"name":"Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica J.","family":"Howell","sequence":"additional","affiliation":[{"name":"Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Asara","sequence":"additional","affiliation":[{"name":"Division of Signal Transduction, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan D.","family":"Manning","sequence":"additional","affiliation":[{"name":"Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.017"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20110682"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.07.007"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.06.022"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080281"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.352"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.17.6139-6149.2003"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(78)51019-7"},{"key":"e_1_3_2_10_2","first-page":"3088","article-title":"Dihydroorotate dehydrogenase is a target for the biological effects of leflunomide","volume":"28","author":"Williamson R. 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