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The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation.
- Source :
-
Cell [Cell] 2013 May 23; Vol. 153 (5), pp. 1064-79. - Publication Year :
- 2013
-
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:<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- AMP-Activated Protein Kinases metabolism
Animals
Brain Neoplasms physiopathology
Caenorhabditis elegans genetics
Cell Survival
Cell Transformation, Neoplastic
Elongation Factor 2 Kinase genetics
Food Deprivation
Glioblastoma physiopathology
HeLa Cells
Humans
Mice
Mice, Nude
NIH 3T3 Cells
Neoplasm Transplantation
Peptide Elongation Factor 2 metabolism
Transplantation, Heterologous
Caenorhabditis elegans metabolism
Elongation Factor 2 Kinase metabolism
Neoplasms physiopathology
Peptide Chain Elongation, Translational
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 153
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 23706743
- Full Text :
- https://doi.org/10.1016/j.cell.2013.04.055