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; 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

doi:10.1016/j.cell.2013.04.055

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 SmithXiaochong 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

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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

Originele taal-2	Engels
Pagina's (van-tot)	1064
Aantal pagina's	1
Tijdschrift	Cell
Volume	153
Nummer van het tijdschrift	5
DOI's	https://doi.org/10.1016/j.cell.2013.04.055
Status	Gepubliceerd - 23 mei 2013
Extern gepubliceerd	Ja

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Leprivier, G., Remke, M., Rotblat, B., Dubuc, A., Mateo, A. R. F., Kool, M., Agnihotri, S., El-Naggar, A., Yu, B., Prakash Somasekharan, S., Faubert, B., Bridon, G., Tognon, C. E., Mathers, J., Thomas, R., Li, A., Barokas, A., Kwok, B., Bowden, M., ... Sorensen, P. H. (2013). XThe eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell, 153(5), 1064. https://doi.org/10.1016/j.cell.2013.04.055

@article{69885a0cef7441499d1c0345266b1797,

title = "XThe eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation",

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",

author = "Gabriel Leprivier and Marc Remke and Barak Rotblat and Adrian Dubuc and Mateo, {Abigail Rachele F.} and Marcel Kool and Sameer Agnihotri and Amal El-Naggar and Bin Yu and {Prakash Somasekharan}, Syam and Brandon Faubert and Ga{\"e}lle Bridon and Tognon, {Cristina E.} and Joan Mathers and Ryan Thomas and Amy Li and Adi Barokas and Brian Kwok and Mary Bowden and Stephanie Smith and Xiaochong Wu and Andrey Korshunov and Thomas Hielscher and Northcott, {Paul A.} and Galpin, {Jason D.} and Ahern, {Christopher A.} and Ye Wang and McCabe, {Martin G.} and Collins, {V. Peter} and Jones, {Russell G.} and Michael Pollak and Olivier Delattre and Gleave, {Martin E.} and Eric Jan and Pfister, {Stefan M.} and Proud, {Christopher G.} and Derry, {W. Brent} and Taylor, {Michael D.} and Sorensen, {Poul H.}",

note = "Funding Information: We thank T. Tang, M. Robertson, and C. Chow for technical assistance and B. Fonseca (McGill University), S. Aparicio, S. Mullaly, T. Ng (UBC), J.A. Pospisilik, and R. Teperino (Max Planck Institute, Freiburg) for helpful discussions. This work was supported by the Canadian Cancer Society Research Institute and the British Columbia Cancer Foundation (to P.H.S.) through generous donations from Team Finn and other riders in the Ride to Conquer Cancer and by the National Institutes of Health (CA159859), the Terry Fox Research Institute, and the Pediatric Brain Tumor Foundation (to M.D.T.). ",

year = "2013",

month = may,

day = "23",

doi = "10.1016/j.cell.2013.04.055",

language = "English",

volume = "153",

pages = "1064",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "5",

}

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, nr. 5, blz. 1064. https://doi.org/10.1016/j.cell.2013.04.055

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.

N1 - Funding Information: We thank T. Tang, M. Robertson, and C. Chow for technical assistance and B. Fonseca (McGill University), S. Aparicio, S. Mullaly, T. Ng (UBC), J.A. Pospisilik, and R. Teperino (Max Planck Institute, Freiburg) for helpful discussions. This work was supported by the Canadian Cancer Society Research Institute and the British Columbia Cancer Foundation (to P.H.S.) through generous donations from Team Finn and other riders in the Ride to Conquer Cancer and by the National Institutes of Health (CA159859), the Terry Fox Research Institute, and the Pediatric Brain Tumor Foundation (to M.D.T.).

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

UR - http://www.scopus.com/inward/record.url?scp=84878271546&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2013.04.055

DO - 10.1016/j.cell.2013.04.055

M3 - Article

C2 - 23706743

AN - SCOPUS:84878271546

SN - 0092-8674

VL - 153

SP - 1064

JO - Cell

JF - Cell

IS - 5

ER -

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

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