Elongation factor 2 kinase promotes cell survival by inhibiting protein synthesis without inducing autophagy

Cellular Signalling

Volumn 28, Issue 4, 2016, Pages 284-293

  Moore, Claire E J ^a,b   Wang, Xuemin ^a,b,c   Xie, Jianling ^a,b   Pickford, Jo ^a   Barron, John ^a   Regufe da Mota, Sergio ^a,e   Versele, Matthias ^d   Proud, Christopher G ^a,b,c  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b SOUTH AUSTRALIAN HEALTH AND MEDICAL RESEARCH INSTITUTE   (Australia)

^c UNIVERSITY OF ADELAIDE   (Australia)

^d JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^e SOUTHAMPTON GENERAL HOSPITAL   (United Kingdom)

Author keywords

EEF2K; Glucose starvation; Translation

Indexed keywords

ELONGATION FACTOR 2 KINASE; GLUCOSE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; RAPAMYCIN; EEF2K PROTEIN, MOUSE; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; TARGET OF RAPAMYCIN KINASE;

ANIMAL CELL; ARTICLE; AUTOPHAGY; CANCER CELL; CELL PROTECTION; CELL SURVIVAL; CONTROLLED STUDY; EMBRYO; HUMAN; HUMAN CELL; INTRACELLULAR SIGNALING; LUNG CARCINOMA; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; STARVATION; ANIMAL; ENZYMOLOGY; FIBROBLAST; GENETICS; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY;

ANIMALS; AUTOPHAGY; CELL SURVIVAL; ELONGATION FACTOR 2 KINASE; FIBROBLASTS; MICE; MICE, KNOCKOUT; MULTIPROTEIN COMPLEXES; PROTEIN BIOSYNTHESIS; TOR SERINE-THREONINE KINASES;

EID: 84955445028     PISSN: 08986568     EISSN: 18733913     Source Type: Journal    
DOI: 10.1016/j.cellsig.2016.01.005     Document Type: Article

References (43)

1. Leprivier G., Remke M., Rotblat B., Dubuc A., Mateo A.R., Kool M., Agnihotri S., El-Naggar A., Yu B., Prakash S.S., Faubert B., Bridon G., Tognon C.E., Mathers J., Thomas R., Li A., Barokas A., Kwok B., Bowden M., Smith S., Wu X., Korshunov A., Hielscher T., Northcott P.A., Galpin J.D., Ahern C.A., Wang Y., McCabe M.G., Collins V.P., Jones R.G., Pollak M., Delattre O., Gleave M.E., Jan E., Pfister S.M., Proud C.G., Derry W.B., Taylor M.D., Sorensen P.H. The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell 2013, 153:1064-1079.
2. Kenney J.W., Moore C.E., Wang X., Proud C.G. Eukaryotic elongation factor 2 kinase, an unusual enzyme with multiple roles. Adv. Biol. Regul. 2014, 55:15-27.
3. Ryazanov A.G., Pavur K.S., Dorovkov M.V. Alpha kinases: a new class of protein kinases with a novel catalytic domain. Curr. Biol. 1999, 9:R43-R45.
4. Pyr Dit Ruys S., Wang X., Smith E.M., Herinckx G., Hussain N., Rider M.H., Vertommen D., Proud C.G. Identification of autophosphorylation sites in eukaryotic elongation factor-2 kinase. Biochem. J. 2012, 442:681-692.
5. Tavares C.D., O'Brien J.P., Abramczyk O., Devkota A.K., Shores K.S., Ferguson S.B., Kaoud T.S., Warthaka M., Marshall K.D., Keller K.M., Zhang Y., Brodbelt J.S., Ozpolat B., Dalby K.N. Calcium/calmodulin stimulates the autophosphorylation of elongation factor 2 kinase on Thr-348 and Ser-500 to regulate its activity and calcium dependence. Biochemistry 2012, 51:2232-2245.
6. Buttgereit F., Brand M.D. A hierarchy of ATP-consuming processes in mammalian cells. Biochem. J. 1995, 312:163-167.
7. Horman S., Browne G.J., Krause U., Patel J.V., Vertommen D., Bertrand L., Lavoinne A., Hue L., Proud C.G., Rider M.H. Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr. Biol. 2002, 12:1419-1423.
8. Liu J.C., Voisin V., Wang S., Wang D.Y., Jones R.A., Datti A., Uehling D., Al-Awar R., Egan S.E., Bader G.D., Tsao M., Mak T.W., Zacksenhaus E. Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K. EMBO Mol. Med. 2014, 6:1542-1560.
9. Dunlop E.A., Tee A.R. mTOR and autophagy: a dynamic relationship governed by nutrients and energy. Semin. Cell Dev. Biol. 2014.
10. Alers S., Loffler A.S., Wesselborg S., Stork B. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol. Cell. Biol. 2012, 32:2-11.
11. Kim J., Kundu M., Viollet B., Guan K.L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 2011, 13:132-141.
12. Egan D., Kim J., Shaw R.J., Guan K.L. The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR. Autophagy 2011, 7:643-644.
13. Hardie D.G. AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev. 2011, 25:1895-1908.
14. Roach P.J. AMPK→ULK1→autophagy. Mol. Cell. Biol. 2011, 31:3082-3084.
15. Cheng Y., Ren X., Zhang Y., Patel R., Sharma A., Wu H., Robertson G.P., Yan L., Rubin E., Yang J.M. eEF-2 kinase dictates cross-talk between autophagy and apoptosis induced by Akt inhibition, thereby modulating cytotoxicity of novel Akt inhibitor MK-2206. Cancer Res. 2011, 71:2654-2663.
16. Wu H., Zhu H., Liu D.X., Niu T.K., Ren X., Patel R., Hait W.N., Yang J.M. Silencing of elongation factor-2 kinase potentiates the effect of 2-deoxy-d-glucose against human glioma cells through blunting of autophagy. Cancer Res. 2009, 69:2453-2460.
17. Wu H., Yang J.M., Jin S., Zhang H., Hait W.N. Elongation factor-2 kinase regulates autophagy in human glioblastoma cells. Cancer Res. 2006, 66:3015-3023.
18. Py B.F., Boyce M., Yuan J. A critical role of eEF-2K in mediating autophagy in response to multiple cellular stresses. Autophagy 2009, 5:393-396.
19. Kimmelman A.C. The dynamic nature of autophagy in cancer. Genes Dev. 2011, 25:1999-2010.
20. Mathew R., White E. Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night. Curr. Opin. Genet. Dev. 2011, 21:113-119.
21. Kenney, J. W., Genheden, M., Moon, K.-M., Foster, L. J., and Proud, C. G. eEF2K regulates the synthesis of microtubule-related proteins in neurons. J. Neurochem., (published online doi: 10.1111/jnc.1340. 2015).
22. Wang X., Regufe da M.S., Liu R., Moore C.E., Xie J., Lanucara F., Agarwala U., Pyr Dit R.S., Vertommen D., Rider M.H., Eyers C.E., Proud C.G. Eukaryotic elongation factor 2 kinase activity is controlled by multiple inputs from oncogenic signaling. Mol. Cell. Biol. 2014, 34:4088-4103.
23. Devkota A.K., Tavares C.D., Warthaka M., Abramczyk O., Marshall K.D., Kaoud T.S., Gorgulu K., Ozpolat B., Dalby K.N. Investigating the kinetic mechanism of inhibition of elongation factor 2 kinase by NH125: evidence of a common in vitro artifact. Biochemistry 2012, 51:2100-2112.
24. Chen Z., Gopalakrishnan S.M., Bui M.H., Soni N.B., Warrior U., Johnson E.F., Donnelly J.B., Glaser K.B. 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) induces phosphorylation of eukaryotic elongation factor-2 (eEF2): a cautionary note on the anticancer mechanism of an eEF2 kinase inhibitor. J. Biol. Chem. 2011, 286:43951-43958.
25. Wang X., Xie J., da Mota S.R., Moore C.E., Proud C.G. Regulated stability of eukaryotic elongation factor 2 kinase requires intrinsic but not ongoing activity. Biochem. J. 2015, 467:321-331.
26. Browne G.J., Finn S.G., Proud C.G. Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. J. Biol. Chem. 2004, 279:12220-12231.
27. Hardie D.G., Ross F.A., Hawley S.A. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 2012, 13:251-262.
28. Fang F.D., Zuo J., Wu G.Y., Yi M.G. New evidence for the inhibition by harringtonine in the formation of the first peptide bond in protein synthesis. Sci. Sinica 1985, 28:512-516.
29. Huang M.T. Harringtonine, an inhibitor of initiation of protein biosynthesis. Mol. Pharmacol. 1975, 11:511-519.
30. Price D.J., Nemenoff R.A., Avruch J. Purification of a hepatic S6 kinase from cycloheximide-treated rats. J. Biol. Chem. 1989, 264:13833.
31. Chresta C.M., Davies B.R., Hickson I., Harding T., Cosulich S., Critchlow S.E., Vincent J.P., Ellston R., Jones D., Sini P., James D., Howard Z., Dudley P., Hughes G., Smith L., Maguire S., Hummersone M., Malagu K., Menear K., Jenkins R., Jacobsen M., Smith G.C., Guichard S., Pass M. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res. 2010, 70:288-298.
32. Kabeya Y., Mizushima N., Yamamoto A., Oshitani-Okamoto S., Ohsumi Y., Yoshimori T. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J. Cell Sci. 2004, 117:2805-2812.
33. Mizushima N., Yoshimori T. How to interpret LC3 immunoblotting. Autophagy 2007, 3:542-545.
34. Dennis P.B., Mercer C.A. The GST-BHMT assay and related assays for autophagy. Methods Enzymol. 2009, 452:97-118.
35. Hirai H., Sootome H., Nakatsuru Y., Miyama K., Taguchi S., Tsujioka K., Ueno Y., Hatch H., Majumder P.K., Pan B.S., Kotani H. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol. Cancer Ther. 2010, 9:1956-1967.
36. Jewell J.L., Russell R.C., Guan K.L. Amino acid signalling upstream of mTOR. Nat. Rev. Mol. Cell Biol. 2013, 14:133-139.
37. Choo A.Y., Kim S.G., Vander Heiden M.G., Mahoney S.J., Vu H., Yoon S.O., Cantley L.C., Blenis J. Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply. Mol. Cell 2010, 38:487-499.
38. Redpath N.T., Foulstone E.J., Proud C.G. Regulation of translation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway. EMBO J. 1996, 15:2291-2297.
39. Moore C.E., Mikolajek H., Regufe da Mota S., Wang X., Kenney J.W., Werner J.M., Proud C.G. Elongation factor 2 kinase is regulated by proline hydroxylation and protects cells during hypoxia. Mol. Cell. Biol. 2015, 35:1788-1804. (Ref Type: Generic).
40. Hait W.N., Wu H., Jin S., Yang J.M. Elongation factor-2 kinase: its role in protein synthesis and autophagy. Autophagy 2006, 2:294-296.
41. Manning B.D. Adaptation to starvation: translating a matter of life or death. Cancer Cell 2013, 23:713-715.
42. Green D.R., Galluzzi L., Kroemer G. Cell biology. Metabolic control of cell death. Science 2014, 345:1250256.
43. Xie C.M., Liu X.Y., sham K.W., Lai J.M., Cheng C.H. Silencing of EEF2K (eukaryotic elongation factor-2 kinase) reveals AMPK-ULK1-dependent autophagy in colon cancer cells. Autophagy 2014, 10:1495-1508.