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The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation

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 pa...

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Main Authors: Leprivier, Gabriel (Author) , Remke, Marc (Author) , Rotblat, Barak (Author) , Dubuc, Adrian (Author) , Mateo, Abigail-Rachele F. (Author) , Kool, Marcel (Author) , Agnihotri, Sameer (Author) , El-Naggar, Amal (Author) , Yu, Bin (Author) , Prakash Somasekharan, Syam (Author) , Faubert, Brandon (Author) , Bridon, Gaëlle (Author) , Tognon, Cristina E. (Author) , Mathers, Joan (Author) , Thomas, Ryan (Author) , Li, Amy (Author) , Barokas, Adi (Author) , Kwok, Brian (Author) , Bowden, Mary (Author) , Smith, Stephanie (Author) , Wu, Xiaochong (Author) , Korshunov, Andrey (Author) , Hielscher, Thomas (Author) , Northcott, Paul A. (Author) , Galpin, Jason D. (Author) , Ahern, Christopher A. (Author) , Wang, Ye (Author) , McCabe, Martin G. (Author) , Collins, V. Peter (Author) , Jones, Russell G. (Author) , Pollak, Michael (Author) , Delattre, Olivier (Author) , Gleave, Martin E. (Author) , Jan, Eric (Author) , Pfister, Stefan (Author) , Proud, Christopher G. (Author) , Derry, W. Brent (Author) , Taylor, Michael D. (Author) , Sorensen, Poul H. (Author)
Format: Article (Journal)
Language:English
Published: May 23, 2013
In: Cell
Year: 2013, Volume: 153, Issue: 5, Pages: 1064-1079
ISSN:1097-4172
DOI:10.1016/j.cell.2013.04.055
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cell.2013.04.055
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867413005321
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Author Notes: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, Gaëlle 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, and Poul H. Sorensen
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Summary: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.
Item Description:Gesehen am 26.01.2022
Physical Description:Online Resource
ISSN:1097-4172
DOI:10.1016/j.cell.2013.04.055

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