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eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition

Title:

eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition

Osborne, M. J., Volpon, L., Kornblatt, Jack A., Culjkovic-Kraljacic, B., Baguet, A. and Borden, K. L. B. (2013) eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition. Proceedings of the National Academy of Sciences, 110 (10). pp. 3877-3882. ISSN 0027-8424

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Official URL: http://dx.doi.org/10.1073/pnas.1216862110

Abstract

Recognition of the methyl-7-guanosine (m7G) cap structure on mRNA is an essential feature of mRNA metabolism and thus gene expression. Eukaryotic translation initiation factor 4E (eIF4E) promotes translation, mRNA export, proliferation, and oncogenic transformation dependent on this cap-binding activity. eIF4E–cap recognition is mediated via complementary charge interactions of the positively charged m7G cap between the negative π-electron clouds from two aromatic residues. Here, we demonstrate that a variant subfamily, eIF4E3, specifically binds the m7G cap in the absence of an aromatic sandwich, using instead a different spatial arrangement of residues to provide the necessary electrostatic and van der Waals contacts. Contacts are much more extensive between eIF4E3–cap than other family members. Structural analyses of other cap-binding proteins indicate this recognition mode is atypical. We demonstrate that eIF4E3 relies on this cap-binding activity to act as a tumor suppressor, competing with the growth-promoting functions of eIF4E. In fact, reduced eIF4E3 in high eIF4E cancers suggests that eIF4E3 underlies a clinically relevant inhibitory mechanism that is lost in some malignancies. Taken together, there is more structural plasticity in cap recognition than previously thought, and this is physiologically relevant.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Article
Refereed:Yes
Authors:Osborne, M. J. and Volpon, L. and Kornblatt, Jack A. and Culjkovic-Kraljacic, B. and Baguet, A. and Borden, K. L. B.
Journal or Publication:Proceedings of the National Academy of Sciences
Date:2013
Digital Object Identifier (DOI):10.1073/pnas.1216862110
ID Code:978229
Deposited By: DAVID MACAULAY
Deposited On:22 Jan 2014 17:26
Last Modified:18 Jan 2018 17:46
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