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Article

Elongation Factor 2 Kinase Is Regulated by Proline Hydroxylation and Protects Cells during Hypoxia

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Pages 1788-1804 | Received 03 Dec 2014, Accepted 01 Mar 2015, Published online: 20 Mar 2023

REFERENCES

  • Ryazanov AG, Rudkin BB, Spirin AS. 1991. Regulation of protein synthesis at the elongation stage. New insights into the control of gene expression in eukaryotes. FEBS Lett 285:170–175.
  • Carlberg U, Nilsson A, Nygard O. 1990. Functional properties of phosphorylated elongation factor 2. Eur J Biochem 191:639–645. http://dx.doi.org/10.1111/j.1432-1033.1990.tb19169.x.
  • Kruiswijk F, Yuniati L, Magliozzi R, Low TY, Lim R, Bolder R, Mohammed S, Proud CG, Heck AJ, Pagano M, Guardavaccaro D. 2012. Coupled activation and degradation of eEF2K regulates protein synthesis in response to genotoxic stress. Sci Signal 5:ra40. http://dx.doi.org/10.1126/scisignal.2002718.
  • Leprivier G, Remke M, Rotblat B, Dubuc A, Mateo AR, Kool M, Agnihotri S, El-Naggar A, Yu B, Prakash SS, 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. The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell 153:1064–1079. http://dx.doi.org/10.1016/j.cell.2013.04.055.
  • Redpath NT, Foulstone EJ, Proud CG. 1996. Regulation of translation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway. EMBO J 15:2291–2297.
  • Diggle TA, Seehra CK, Hase S, Redpath NT. 1999. Analysis of the domain structure of elongation factor-2 kinase by mutagenesis. FEBS Lett 457:189–192. http://dx.doi.org/10.1016/S0014-5793(99)01034-0.
  • Pavur KS, Petrov AN, Ryazanov AG. 2000. Mapping the functional domains of elongation factor-2 kinase. Biochemistry 39:12216–12224. http://dx.doi.org/10.1021/bi0007270.
  • Drennan D, Ryazanov AG. 2004. Alpha-kinases: analysis of the family and comparison with conventional protein kinases. Prog Biophys Mol Biol 85:1–32. http://dx.doi.org/10.1016/S0079-6107(03)00060-9.
  • Middelbeek J, Clark K, Venselaar H, Huynen MA, van Leeuwen FN. 2010. The alpha-kinase family: an exceptional branch on the protein kinase tree. Cell Mol Life Sci 67:875–890. http://dx.doi.org/10.1007/s00018-009-0215-z.
  • Hardie DG, Ross FA, Hawley SA. 2012. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 13:251–262. http://dx.doi.org/10.1038/nrm3311.
  • Browne GJ, Finn SG, Proud CG. 2004. 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 279:12220–12231. http://dx.doi.org/10.1074/jbc.M309773200.
  • Horman S, Browne GJ, Krause U, Patel JV, Vertommen D, Bertrand L, Lavoinne A, Hue L, Proud CG, Rider MH. 2002. Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol 12:1419–1423. http://dx.doi.org/10.1016/S0960-9822(02)01077-1.
  • Kaelin WG Jr, Ratcliffe PJ. 2008. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30:393–402. http://dx.doi.org/10.1016/j.molcel.2008.04.009.
  • Gorres KL, Raines RT. 2010. Prolyl 4-hydroxylase. Crit Rev Biochem Mol Biol 45:106–124. http://dx.doi.org/10.3109/10409231003627991.
  • Connolly E, Braunstein S, Formenti S, Schneider RJ. 2006. Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells. Mol Cell Biol 26:3955–3965. http://dx.doi.org/10.1128/MCB.26.10.3955-3965.2006.
  • Terai K, Hiramoto Y, Masaki M, Sugiyama S, Kuroda T, Hori M, Kawase I, Hirota H. 2005. AMP-activated protein kinase protects cardiomyocytes against hypoxic injury through attenuation of endoplasmic reticulum stress. Mol Cell Biol 25:9554–9575. http://dx.doi.org/10.1128/MCB.25.21.9554-9575.2005.
  • Romero-Ruiz A, Bautista L, Navarro V, Heras-Garvin A, March-Diaz R, Castellano A, Gomez-Diaz R, Castro MJ, Berra E, Lopez-Barneo J, Pascual A. 2012. Prolyl hydroxylase-dependent modulation of eukaryotic elongation factor 2 activity and protein translation under acute hypoxia. J Biol Chem 287:9651–9658. http://dx.doi.org/10.1074/jbc.M111.299180.
  • Knebel A, Morrice N, Cohen P. 2001. A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. EMBO J 20:4360–4369. http://dx.doi.org/10.1093/emboj/20.16.4360.
  • Hall-Jackson CA, Cross DA, Morrice N, Smythe C. 1999. ATR is a caffeine-sensitive, DNA-activated protein kinase with a substrate specificity distinct from DNA-PK. Oncogene 18:6707–6713. http://dx.doi.org/10.1038/sj.onc.1203077.
  • Laderoute KR, Amin K, Calaoagan JM, Knapp M, Le T, Orduna J, Foretz M, Viollet B. 2006. 5′-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Mol Cell Biol 26:5336–5347. http://dx.doi.org/10.1128/MCB.00166-06.
  • Wong HK, Fricker M, Wyttenbach A, Villunger A, Michalak EM, Strasser A, Tolkovsky AM. 2005. Mutually exclusive subsets of BH3-only proteins are activated by the p53 and c-Jun N-terminal kinase/c-Jun signaling pathways during cortical neuron apoptosis induced by arsenite. Mol Cell Biol 25:8732–8747. http://dx.doi.org/10.1128/MCB.25.19.8732-8747.2005.
  • Bradford MM. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 77:248–254.
  • Browne GJ, Proud CG. 2004. A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin. Mol Cell Biol 24:2986–2997. http://dx.doi.org/10.1128/MCB.24.7.2986-2997.2004.
  • Pigott CR, Mikolajek H, Moore CE, Finn SJ, Phippen CW, Werner JM, Proud CG. 2012. Insights into the regulation of eukaryotic elongation factor 2 kinase and the interplay between its domains. Biochem J 442:105–118. http://dx.doi.org/10.1042/BJ20111536.
  • Moore CE, da Mota SR, Mikolajek H, Proud CG. 2014. A Conserved loop in the catalytic domain of eukaryotic elongation factor 2 kinase plays a key role in its substrate specificity. Mol Cell Biol 34:2294–2307. http://dx.doi.org/10.1128/MCB.00388-14.
  • Speicher KD, Kolbas O, Harper S, Speicher DW. 2000. Systematic analysis of peptide recoveries from in-gel digestions for protein identifications in proteome studies. J Biomol Tech 11:74–86.
  • Hong-Brown LQ, Brown CR, Huber DS, Lang CH. 2008. Lopinavir impairs protein synthesis and induces eEF2 phosphorylation via the activation of AMP-activated protein kinase. J Cell Biochem 105:814–823. http://dx.doi.org/10.1002/jcb.21882.
  • Majmundar AJ, Wong WJ, Simon MC. 2010. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell 40:294–309. http://dx.doi.org/10.1016/j.molcel.2010.09.022.
  • Wiseman SL, Shimizu Y, Palfrey C, Nairn AC. 2013. Proteasomal degradation of eukaryotic elongation factor-2 kinase (EF2K) is regulated by cAMP-PKA signaling and the SCFbetaTRCP ubiquitin E3 ligase. J Biol Chem 288:17803–17811. http://dx.doi.org/10.1074/jbc.M113.477182.
  • Knebel A, Haydon CE, Morrice N, Cohen P. 2002. Stress-induced regulation of eEF2 kinase by SB203580-sensitive and -insensitive pathways. Biochem J 367:525–532. http://dx.doi.org/10.1042/BJ20020916.
  • Clark K, MacKenzie KF, Petkevicius K, Kristariyanto Y, Zhang J, Choi HG, Peggie M, Plater L, Pedrioli PG, McIver E, Gray NS, Arthur JS, Cohen P. 2012. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci U S A 109:16986–16991. http://dx.doi.org/10.1073/pnas.1215450109.
  • Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ. 2008. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30:214–226. http://dx.doi.org/10.1016/j.molcel.2008.03.003.
  • Inoki K, Zhu T, Guan KL. 2003. TSC2 mediates cellular energy response to control cell growth and survival. Cell 115:577–590. http://dx.doi.org/10.1016/S0092-8674(03)00929-2.
  • Robinson A, Keely S, Karhausen J, Gerich ME, Furuta GT, Colgan SP. 2008. Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition. Gastroenterology 134:145–155. http://dx.doi.org/10.1053/j.gastro.2007.09.033.
  • Chresta CM, Davies BR, Hickson I, Harding T, Cosulich S, Critchlow SE, Vincent JP, 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 GC, Guichard S, Pass M. 2010. 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 70:288–298. http://dx.doi.org/10.1158/0008-5472.CAN-09-1751.
  • Tiainen M, Vaahtomeri K, Ylikorkala A, Makela TP. 2002. Growth arrest by the LKB1 tumor suppressor: induction of p21(WAF1/CIP1). Hum Mol Genet 11:1497–1504. http://dx.doi.org/10.1093/hmg/11.13.1497.
  • Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG Jr. 2004. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 18:2893–2904. http://dx.doi.org/10.1101/gad.1256804.
  • Duran RV, Mackenzie ED, Boulahbel H, Frezza C, Heiserich L, Tardito S, Bussolati O, Rocha S, Hall MN, Gottlieb E. 2012. HIF-independent role of prolyl hydroxylases in the cellular response to amino acids. Oncogene 32:4549–4556. http://dx.doi.org/10.1038/onc.2012.465.
  • Lee K, Zhang H, Qian DZ, Rey S, Liu JO, Semenza GL. 2009. Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci U S A 106:17910–17915. http://dx.doi.org/10.1073/pnas.0909353106.
  • Redpath NT, Proud CG. 1993. Cyclic AMP-dependent protein kinase phosphorylates rabbit reticulocyte elongation factor-2 kinase and induces calcium-independent activity. Biochem J 293:31–34.
  • Arora S, Yang JM, Hait WN. 2005. Identification of the ubiquitin-proteasome pathway in the regulation of the stability of eukaryotic elongation factor-2 kinase. Cancer Res 65:3806–3810. http://dx.doi.org/10.1158/0008-5472.CAN-04-4036.
  • Gobeil S, Boucher CC, Nadeau D, Poirier GG. 2001. Characterization of the necrotic cleavage of poly(ADP-ribose) polymerase (PARP-1): implication of lysosomal proteases. Cell Death Differ 8:588–594. http://dx.doi.org/10.1038/sj.cdd.4400851.
  • Lehane C, Guelzow T, Zenker S, Erxleben A, Schwer CI, Heimrich B, Buerkle H, Humar M. 2013. Carbimazole is an inhibitor of protein synthesis and protects from neuronal hypoxic damage in vitro. J Pharmacol Exp Ther 347:781–793. http://dx.doi.org/10.1124/jpet.113.205989.
  • Buttgereit F, Brand MD. 1995. A hierarchy of ATP-consuming processes in mammalian cells. Biochem J 312:163–167.
  • Uniacke J, Holterman CE, Lachance G, Franovic A, Jacob MD, Fabian MR, Payette J, Holcik M, Pause A, Lee S. 2012. An oxygen-regulated switch in the protein synthesis machinery. Nature 486:126–129. http://dx.doi.org/10.1038/nature11055.
  • Cummins EP, Berra E, Comerford KM, Ginouves A, Fitzgerald KT, Seeballuck F, Godson C, Nielsen JE, Moynagh P, Pouyssegur J, Taylor CT. 2006. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. Proc Natl Acad Sci U S A 103:18154–18159. http://dx.doi.org/10.1073/pnas.0602235103.
  • Loenarz C, Sekirnik R, Thalhammer A, Ge W, Spivakovsky E, Mackeen MM, McDonough MA, Cockman ME, Kessler BM, Ratcliffe PJ, Wolf A, Schofield CJ. 2014. Hydroxylation of the eukaryotic ribosomal decoding center affects translational accuracy. Proc Natl Acad Sci U S A 111:4019–4024. http://dx.doi.org/10.1073/pnas.1311750111.
  • Singleton RS, Liu-Yi P, Formenti F, Ge W, Sekirnik R, Fischer R, Adam J, Pollard PJ, Wolf A, Thalhammer A, Loenarz C, Flashman E, Yamamoto A, Coleman ML, Kessler BM, Wappner P, Schofield CJ, Ratcliffe PJ, Cockman ME. 2014. OGFOD1 catalyzes prolyl hydroxylation of RPS23 and is involved in translation control and stress granule formation. Proc Natl Acad Sci U S A 111:4031–4036. http://dx.doi.org/10.1073/pnas.1314482111.
  • Diggle TA, Subkhankulova T, Lilley KS, Shikotra N, Willis AE, Redpath NT. 2001. Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity. Biochem J 353:621–626. http://dx.doi.org/10.1042/0264-6021:3530621.
  • Liu JC, Voisin V, Wang S, Wang DY, Jones RA, Datti A, Uehling D, Al-Awar R, Egan SE, Bader GD, Tsao M, Mak TW, Zacksenhaus E. 2014. Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K. EMBO Mol Med 6:1542–1560. http://dx.doi.org/10.15252/emmm.201404402.

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