mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry
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Dai-2011-mTOR phosphorylates.pdf
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Author(s)
Dai, Ning
Rapley, Joseph
Angel, Matthew
Yanik, Mehmet Fatih
Blower, Michael D.
Avruch, Joseph
Date Issued
May 2011
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory Press
Citation
Dai, N., J. Rapley, M. Angel, M. F. Yanik, M. D. Blower, and J. Avruch. “mTOR Phosphorylates IMP2 to Promote IGF2 mRNA Translation by Internal Ribosomal Entry.” Genes & Development 25, no. 11 (June 1, 2011): 1159–1172.
Version
Final published version
Abstract
Variants 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.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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Article is available under a Creative Commons license; see publisher’s site for details.
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DOI of Published Version
https://doi.org/10.1101/gad.2042311
