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The eIF4E RNA regulon promotes the Akt signaling pathway

Eukaryotic initiation factor 4E (eIF4E) promotes cellular proliferation and can rescue cells from apoptotic stimuli such as serum starvation. However, the mechanisms underlying apoptotic rescue are not well understood. In this study, we demonstrate that eIF4E overexpression leads to enhanced surviva...

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Detalles Bibliográficos
Autores principales: Culjkovic, Biljana, Tan, Keith, Orolicki, Slobodanka, Amri, Abdellatif, Meloche, Sylvain, Borden, Katherine L.B.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2287285/
https://www.ncbi.nlm.nih.gov/pubmed/18391071
http://dx.doi.org/10.1083/jcb.200707018
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author Culjkovic, Biljana
Tan, Keith
Orolicki, Slobodanka
Amri, Abdellatif
Meloche, Sylvain
Borden, Katherine L.B.
author_facet Culjkovic, Biljana
Tan, Keith
Orolicki, Slobodanka
Amri, Abdellatif
Meloche, Sylvain
Borden, Katherine L.B.
author_sort Culjkovic, Biljana
collection PubMed
description Eukaryotic initiation factor 4E (eIF4E) promotes cellular proliferation and can rescue cells from apoptotic stimuli such as serum starvation. However, the mechanisms underlying apoptotic rescue are not well understood. In this study, we demonstrate that eIF4E overexpression leads to enhanced survival signaling through Akt and that eIF4E requires Akt1 to rescue serum-deprived fibroblasts. Furthermore, a mutant form of eIF4E (W73A), which is messenger RNA (mRNA) export competent but does not promote translation, rescues cells as readily as wild-type eIF4E. We show that eIF4E mediates Akt activation via up-regulation of Nijmegen breakage syndrome 1 (NBS1), a phosphoinositide-3 kinase–Akt pathway upstream activator. Additionally, eIF4E coordinately up-regulates the expression of downstream effectors of the Akt pathway, thereby amplifying Akt signaling effects. A negative regulator of eIF4E, the promyelocytic leukemia protein (PML), suppresses Akt activation and apoptotic rescue. These PML activities likely arise, at least in part, through its inhibition of eIF4E-mediated NBS1 mRNA export. In summary, eIF4E coordinately regulates gene expression to potentiate Akt activation, an activity required for apoptotic rescue.
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spelling pubmed-22872852008-10-07 The eIF4E RNA regulon promotes the Akt signaling pathway Culjkovic, Biljana Tan, Keith Orolicki, Slobodanka Amri, Abdellatif Meloche, Sylvain Borden, Katherine L.B. J Cell Biol Research Articles Eukaryotic initiation factor 4E (eIF4E) promotes cellular proliferation and can rescue cells from apoptotic stimuli such as serum starvation. However, the mechanisms underlying apoptotic rescue are not well understood. In this study, we demonstrate that eIF4E overexpression leads to enhanced survival signaling through Akt and that eIF4E requires Akt1 to rescue serum-deprived fibroblasts. Furthermore, a mutant form of eIF4E (W73A), which is messenger RNA (mRNA) export competent but does not promote translation, rescues cells as readily as wild-type eIF4E. We show that eIF4E mediates Akt activation via up-regulation of Nijmegen breakage syndrome 1 (NBS1), a phosphoinositide-3 kinase–Akt pathway upstream activator. Additionally, eIF4E coordinately up-regulates the expression of downstream effectors of the Akt pathway, thereby amplifying Akt signaling effects. A negative regulator of eIF4E, the promyelocytic leukemia protein (PML), suppresses Akt activation and apoptotic rescue. These PML activities likely arise, at least in part, through its inhibition of eIF4E-mediated NBS1 mRNA export. In summary, eIF4E coordinately regulates gene expression to potentiate Akt activation, an activity required for apoptotic rescue. The Rockefeller University Press 2008-04-07 /pmc/articles/PMC2287285/ /pubmed/18391071 http://dx.doi.org/10.1083/jcb.200707018 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Culjkovic, Biljana
Tan, Keith
Orolicki, Slobodanka
Amri, Abdellatif
Meloche, Sylvain
Borden, Katherine L.B.
The eIF4E RNA regulon promotes the Akt signaling pathway
title The eIF4E RNA regulon promotes the Akt signaling pathway
title_full The eIF4E RNA regulon promotes the Akt signaling pathway
title_fullStr The eIF4E RNA regulon promotes the Akt signaling pathway
title_full_unstemmed The eIF4E RNA regulon promotes the Akt signaling pathway
title_short The eIF4E RNA regulon promotes the Akt signaling pathway
title_sort eif4e rna regulon promotes the akt signaling pathway
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2287285/
https://www.ncbi.nlm.nih.gov/pubmed/18391071
http://dx.doi.org/10.1083/jcb.200707018
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