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

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 & 19 others 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

Research output: Contribution to journalArticle

200 Citations (Scopus)

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

LanguageEnglish
Number of pages1
JournalCell
Volume153
Issue number5
DOIs
Publication statusPublished - 23 May 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Leprivier, G., Remke, M., Rotblat, B., Dubuc, A., Mateo, A. R. F., Kool, M., ... Sorensen, P. H. (2013). XThe eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell, 153(5). https://doi.org/10.1016/j.cell.2013.04.055
Leprivier, Gabriel ; Remke, Marc ; Rotblat, Barak ; Dubuc, Adrian ; Mateo, Abigail Rachele F ; Kool, Marcel ; Agnihotri, Sameer ; El-Naggar, Amal ; Yu, Bin ; Prakash Somasekharan, Syam ; Faubert, Brandon ; Bridon, Gaëlle ; Tognon, Cristina E. ; Mathers, Joan ; Thomas, Ryan ; Li, Amy ; Barokas, Adi ; Kwok, Brian ; Bowden, Mary ; Smith, Stephanie ; Wu, Xiaochong ; Korshunov, Andrey ; Hielscher, Thomas ; Northcott, Paul A. ; Galpin, Jason D. ; Ahern, Christopher A. ; Wang, Ye ; McCabe, Martin G. ; Collins, V. Peter ; Jones, Russell G. ; Pollak, Michael ; Delattre, Olivier ; Gleave, Martin E. ; Jan, Eric ; Pfister, Stefan M. ; Proud, Christopher G. ; Derry, W. Brent ; Taylor, Michael D. ; Sorensen, Poul H. / XThe eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. In: Cell. 2013 ; Vol. 153, No. 5.
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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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Leprivier, G, Remke, M, Rotblat, B, Dubuc, A, Mateo, ARF, Kool, M, Agnihotri, S, El-Naggar, A, Yu, B, Prakash Somasekharan, S, Faubert, B, Bridon, G, Tognon, CE, Mathers, J, Thomas, R, Li, A, Barokas, A, Kwok, B, Bowden, M, Smith, S, Wu, X, Korshunov, A, Hielscher, T, Northcott, PA, Galpin, JD, Ahern, CA, Wang, Y, McCabe, MG, Collins, VP, Jones, RG, Pollak, M, Delattre, O, Gleave, ME, Jan, E, Pfister, SM, Proud, CG, Derry, WB, Taylor, MD & Sorensen, PH 2013, 'XThe eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation', Cell, vol. 153, no. 5. https://doi.org/10.1016/j.cell.2013.04.055

XThe eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. / Leprivier, Gabriel; Remke, Marc; Rotblat, Barak; Dubuc, Adrian; Mateo, Abigail Rachele F; Kool, Marcel; Agnihotri, Sameer; El-Naggar, Amal; Yu, Bin; Prakash Somasekharan, Syam; Faubert, Brandon; Bridon, Gaëlle; Tognon, Cristina E.; Mathers, Joan; Thomas, Ryan; Li, Amy; Barokas, Adi; Kwok, Brian; Bowden, Mary; Smith, Stephanie; Wu, Xiaochong; Korshunov, Andrey; Hielscher, Thomas; Northcott, Paul A.; Galpin, Jason D.; Ahern, Christopher A.; Wang, Ye; McCabe, Martin G.; Collins, V. Peter; Jones, Russell G.; Pollak, Michael; Delattre, Olivier; Gleave, Martin E.; Jan, Eric; Pfister, Stefan M.; Proud, Christopher G.; Derry, W. Brent; Taylor, Michael D.; Sorensen, Poul H.

In: Cell, Vol. 153, No. 5, 23.05.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - XThe eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation

AU - Leprivier, Gabriel

AU - Remke, Marc

AU - Rotblat, Barak

AU - Dubuc, Adrian

AU - Mateo, Abigail Rachele F

AU - Kool, Marcel

AU - Agnihotri, Sameer

AU - El-Naggar, Amal

AU - Yu, Bin

AU - Prakash Somasekharan, Syam

AU - Faubert, Brandon

AU - Bridon, Gaëlle

AU - Tognon, Cristina E.

AU - Mathers, Joan

AU - Thomas, Ryan

AU - Li, Amy

AU - Barokas, Adi

AU - Kwok, Brian

AU - Bowden, Mary

AU - Smith, Stephanie

AU - Wu, Xiaochong

AU - Korshunov, Andrey

AU - Hielscher, Thomas

AU - Northcott, Paul A.

AU - Galpin, Jason D.

AU - Ahern, Christopher A.

AU - Wang, Ye

AU - McCabe, Martin G.

AU - Collins, V. Peter

AU - Jones, Russell G.

AU - Pollak, Michael

AU - Delattre, Olivier

AU - Gleave, Martin E.

AU - Jan, Eric

AU - Pfister, Stefan M.

AU - Proud, Christopher G.

AU - Derry, W. Brent

AU - Taylor, Michael D.

AU - Sorensen, Poul H.

PY - 2013/5/23

Y1 - 2013/5/23

N2 - 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

AB - 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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U2 - 10.1016/j.cell.2013.04.055

DO - 10.1016/j.cell.2013.04.055

M3 - Article

VL - 153

JO - Cell

T2 - Cell

JF - Cell

SN - 0092-8674

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