The EEF2 Kinase Confers Resistance to Nutrient Deprivation by Blocking Translation Elongation

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 May 28

PMID 23706743

Citations 213

Authors

Gabriel Leprivier

Marc Remke

Barak Rotblat

Adrian Dubuc

Abigail-Rachele F Mateo

Marcel Kool

Sameer Agnihotri

Amal El-Naggar

Bin Yu

Syam Prakash Somasekharan

Brandon Faubert

Gaelle Bridon

Cristina E Tognon

Joan Mathers

Ryan Thomas

Amy Li

Adi Barokas

Brian Kwok

Mary Bowden

Stephanie Smith

Xiaochong Wu

Andrey Korshunov

Thomas Hielscher

Paul A Northcott

Jason D Galpin

Christopher A Ahern

Ye Wang

Martin G McCabe

V Peter Collins

Russell G Jones

Michael Pollak

Olivier Delattre

Martin E Gleave

Eric Jan

Stefan M Pfister

Christopher G Proud

W Brent Derry

Michael D Taylor

Poul H Sorensen

Affiliations

Soon will be listed here.

Abstract

Metabolic adaptation is essential for cell survival during nutrient deprivation. We report that eukaryotic elongation factor 2 kinase (eEF2K), which is activated by AMP-kinase (AMPK), confers cell survival under acute nutrient depletion by blocking translation elongation. Tumor cells exploit this pathway to adapt to nutrient deprivation by reactivating the AMPK-eEF2K axis. Adaptation of transformed cells to nutrient withdrawal is severely compromised in cells lacking eEF2K. Moreover, eEF2K knockdown restored sensitivity to acute nutrient deprivation in highly resistant human tumor cell lines. In vivo, overexpression of eEF2K rendered murine tumors remarkably resistant to caloric restriction. Expression of eEF2K strongly correlated with overall survival in human medulloblastoma and glioblastoma multiforme. Finally, C. elegans strains deficient in efk-1, the eEF2K ortholog, were severely compromised in their response to nutrient depletion. Our data highlight a conserved role for eEF2K in protecting cells from nutrient deprivation and in conferring tumor cell adaptation to metabolic stress. PAPERCLIP:

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