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dc.contributor.authorDai, Ning
dc.contributor.authorRapley, Joseph
dc.contributor.authorAngel, Matthew
dc.contributor.authorYanik, M. Fatih
dc.contributor.authorBlower, Michael D.
dc.contributor.authorAvruch, Joseph
dc.date.accessioned2019-10-05T03:28:25Z
dc.date.issued2011
dc.identifier.citationDai, N., J. Rapley, M. Angel, M. F. Yanik, M. D. Blower, and J. Avruch. 2011. “mTOR Phosphorylates IMP2 to Promote IGF2 mRNA Translation by Internal Ribosomal Entry.” Genes & Development 25 (11): 1159–72. https://doi.org/10.1101/gad.2042311.
dc.identifier.issn0890-9369
dc.identifier.issn1549-5477
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41482998*
dc.description.abstractVariants in the IMP2 (insulin-like growth factor 2 [IGF2] mRNA-binding protein 2) gene are implicated in susceptibility to type 2 diabetes. We describe the ability of mammalian target of rapamycin (mTOR) to regulate the cap-independent translation of IGF2 mRNA through phosphorylation of IMP2, an oncofetal RNA-binding protein. IMP2 is doubly phosphorylated in a rapamycin-inhibitable, amino acid-dependent manner in cells and by mTOR in vitro. Double phosphorylation promotes IMP2 binding to the IGF2 leader 3 mRNA 5' untranslated region, and the translational initiation of this mRNA through eIF-4E- and 5' cap-independent internal ribosomal entry. Unexpectedly, the interaction of IMP2 with mTOR complex 1 occurs through mTOR itself rather than through raptor. Whereas depletion of mTOR strongly inhibits IMP2 phosphorylation in cells, comparable depletion of raptor has no effect; moreover, the ability of mTOR to phosphorylate IMP2 in vitro is unaffected by the elimination of raptor. Dual phosphorylation of IMP2 at the mTOR sites is evident in the mouse embryo, likely coupling nutrient sufficiency to IGF2 expression and fetal growth. Doubly phosphorylated IMP2 is also widely expressed in adult tissues, including islets of Langerhans.
dc.language.isoen_US
dc.publisherCold Spring Harbor Laboratory Press
dash.licenseLAA
dc.titlemTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalGenes & Development
dash.depositing.authorAvruch, Joseph::9aac9685759478ee19677d9b77258031::600
dc.date.available2019-10-05T03:28:25Z
dash.workflow.comments1Science Serial ID 41812
dc.identifier.doi10.1101/gad.2042311
dash.source.volume25;11
dash.source.page1159


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