Journal article
The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation
Cell (Cambridge), Vol.153(5), pp.1064-1079
05/23/2013
DOI: 10.1016/j.cell.2013.04.055
PMCID: PMC4395874
PMID: 23706743
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:
Details
- Title: Subtitle
- The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation
- Creators
- Gabriel Leprivier - Department of Molecular Oncology, British Columbia Cancer Research Centre, University of British Columbia (UBC), Vancouver, BC V5Z1L4, CanadaMarc RemkeBarak RotblatAdrian DubucAbigail-Rachele F MateoMarcel KoolSameer AgnihotriAmal El-NaggarBin YuSyam Prakash SomasekharanBrandon FaubertGaëlle BridonCristina E TognonJoan MathersRyan ThomasAmy LiAdi BarokasBrian KwokMary BowdenStephanie SmithXiaochong WuAndrey KorshunovThomas HielscherPaul A NorthcottJason D GalpinChristopher A AhernYe Wang - McGill UniversityMartin G McCabeV Peter CollinsRussell G JonesMichael PollakOlivier DelattreMartin E GleaveEric JanStefan M PfisterChristopher G ProudW Brent DerryMichael D Taylor - University of TorontoPoul H Sorensen
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.153(5), pp.1064-1079
- Publisher
- United States
- DOI
- 10.1016/j.cell.2013.04.055
- PMID
- 23706743
- PMCID
- PMC4395874
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Grant note
- 086688 / Wellcome Trust R01 CA159859 / NCI NIH HHS
- Language
- English
- Date published
- 05/23/2013
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984070620002771
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