{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:21:34Z","timestamp":1781108494819,"version":"3.54.1"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"42","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,10,18]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>MYC<\/jats:italic>\n                    protooncogene is frequently deregulated in human cancers. Here, by screening a kinase-directed library of small inhibitory RNAs, we identify glycogen synthase kinase 3\u03b2 (\n                    <jats:italic>GSK3<\/jats:italic>\n                    \u03b2) as a gene whose inactivation potentiates TNF-related apoptosis-inducing ligand death receptor-mediated apoptosis specifically in MYC-overexpressing cells. Small inhibitory RNA-induced silencing of\n                    <jats:italic>GSK3<\/jats:italic>\n                    \u03b2 prevents phosphorylation of MYC on T58, thereby inhibiting recognition of MYC by the E3 ubiquitin ligase component FBW7. Attenuating the GSK3\u03b2\u2013FBW7 axis results in stabilization of MYC, up-regulation of surface levels of the TNF-related apoptosis-inducing ligand death receptor 5, and potentiation of death receptor 5-induced apoptosis\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . These results identify GSK3\u03b2 and FBW7 as potential cancer therapeutic targets and MYC as a critical substrate in the GSK3\u03b2 survival-signaling pathway. The results also demonstrate paradoxically that MYC-expressing tumors might be treatable by drug combinations that increase rather than decrease MYC oncoprotein function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0505114102","type":"journal-article","created":{"date-parts":[[2005,10,6]],"date-time":"2005-10-06T20:25:11Z","timestamp":1128630311000},"page":"15195-15200","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":91,"title":["A TRAIL receptor-dependent synthetic lethal relationship between\n                    <i>MYC<\/i>\n                    activation and\n                    <i>GSK3\u03b2\/FBW7<\/i>\n                    loss of function"],"prefix":"10.1073","volume":"102","author":[{"given":"Sabine","family":"Rottmann","sequence":"first","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Nasoff","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinn L.","family":"Deveraux","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim C.","family":"Quon","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,10,6]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00697-7"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(02)84004-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","unstructured":"Evan G. 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