Skip to main content

EIF2S1

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

Synonyms

eIF-2A; eIF-2alpha; EIF2S1; Eukaryotic translation initiation factor 2 subunit 1; Eukaryotic translation initiation factor 2 subunit alpha; Eukaryotic translation initiation factor 2, subunit 1 alpha, 35 kDa

Historical Background

Phosphorylation and dephosphorylation of eukaryotic initiation factor 2α (eIF2α) control the initiation of mRNA translation in eukaryotic cells, particularly in response to cellular stress. Early studies on the role of initiation factors in translational control date back to the 1960s. In 1968, Miller and Schweet reported a decrease in reticulocyte ribosomal activity upon salt washing (Miller and Schweet 1968). This first observation led to the isolation of translation initiation factors from rabbit reticulocytes and liver ribosomes (Shafritz et al. 1970). Some years later, it was shown that the eukaryotic translation initiation factor eIF2 consists of three subunits: eIF2α, eIF2β, and eIF2γ (Schreier et al. 1977). In the same year, phosphorylation...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Bellato HM, Hajj GN. Translational control by eIF2alpha in neurons: beyond the stress response. Cytoskeleton. 2016;73:551–65.

    Article  CAS  PubMed  Google Scholar 

  • Colthurst DR, Campbell DG, Proud CG. Structure and regulation of eukaryotic initiation factor eIF-2. Sequence of the site in the alpha subunit phosphorylated by the haem-controlled repressor and by the double-stranded RNA-activated inhibitor. Eur J Biochem/FEBS. 1987;166:357–63.

    Article  CAS  Google Scholar 

  • Devisscher L, Vieri M, Logue SE, Panse J, Geerts A, van Vlierberghe H, Chevet E, Gorman AM, Samali A, Kharabi Masouleh B. Targeting the angio-proteostasis network: combining the forces against cancer. Pharmacol Ther. 2016;167:1–12.

    Article  CAS  PubMed  Google Scholar 

  • Dhaliwal S, Hoffman DW. The crystal structure of the N-terminal region of the alpha subunit of translation initiation factor 2 (eIF2alpha) from Saccharomyces cerevisiae provides a view of the loop containing serine 51, the target of the eIF2alpha-specific kinases. J Mol Biol. 2003;334:187–95.

    Article  CAS  PubMed  Google Scholar 

  • Donnelly N, Gorman AM, Gupta S, Samali A. The eIF2alpha kinases: their structures and functions. Cell Mol Life Sci: CMLS. 2013;70:3493–511.

    Article  CAS  PubMed  Google Scholar 

  • Ernst V, Levin DH, Leroux A, London IM. Site-specific phosphorylation of the alpha subunit of eukaryotic initiation factor eIF-2 by the heme-regulated and double-stranded RNA-activated eIF-2 alpha kinases from rabbit reticulocyte lysates. Proc Natl Acad Sci USA. 1980;77:1286–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farrell PJ, Balkow K, Hunt T, Jackson RJ, Trachsel H. Phosphorylation of initiation factor elF-2 and the control of reticulocyte protein synthesis. Cell. 1977;11:187–200.

    Article  CAS  PubMed  Google Scholar 

  • Harding HP, Zhang Y, Scheuner D, Chen JJ, Kaufman RJ, Ron D. Ppp1r15 gene knockout reveals an essential role for translation initiation factor 2 alpha (eIF2alpha) dephosphorylation in mammalian development. Proc Natl Acad Sci USA. 2009;106:1832–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hart LS, Cunningham JT, Datta T, Dey S, Tameire F, Lehman SL, Qiu B, Zhang H, Cerniglia G, Bi M, Li Y, Gao Y, Liu H, Li C, Maity A, Thomas-Tikhonenko A, Perl AE, Koong A, Fuchs SY, Diehl JA, Mills IG, Ruggero D, Koumenis C. ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth. J Clin Investig. 2012;122:4621–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ito T, Marintchev A, Wagner G. Solution structure of human initiation factor eIF2alpha reveals homology to the elongation factor eEF1B. Structure. 2004;12:1693–704.

    Article  CAS  PubMed  Google Scholar 

  • Jousse C, Oyadomari S, Novoa I, Lu P, Zhang Y, Harding HP, Ron D. Inhibition of a constitutive translation initiation factor 2alpha phosphatase, CReP, promotes survival of stressed cells. J Cell Biol. 2003;163:767–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koumenis C, Naczki C, Koritzinsky M, Rastani S, Diehl A, Sonenberg N, Koromilas A, Wouters BG. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha. Mol Cell Biol. 2002;22:7405–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma T, Trinh MA, Wexler AJ, Bourbon C, Gatti E, Pierre P, Cavener DR, Klann E. Suppression of eIF2alpha kinases alleviates Alzheimer’s disease-related plasticity and memory deficits. Nat Neurosci. 2013;16:1299–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller RL, Schweet R. Isolation of a protein fraction from reticulocyte ribosomes required for de novo synthesis of hemoglobin. Arch Biochem Biophys. 1968;125:632–46.

    Article  CAS  PubMed  Google Scholar 

  • Nonato MC, Widom J, Clardy J. Crystal structure of the N-terminal segment of human eukaryotic translation initiation factor 2alpha. J Biol Chem. 2002;277:17057–61.

    Article  CAS  PubMed  Google Scholar 

  • Pakos-Zebrucka K, Koryga I, Mnich K, Ljuic M, Samali A, Gorman AM. The integrated stress response. EMBO Rep. 2016;17:1374–95. EMBO Reports.

    Google Scholar 

  • Pathak VK, Schindler D, Hershey JW. Generation of a mutant form of protein synthesis initiation factor eIF-2 lacking the site of phosphorylation by eIF-2 kinases. Mol Cell Biol. 1988;8:993–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scheuner D, Song B, McEwen E, Liu C, Laybutt R, Gillespie P, Saunders T, Bonner-Weir S, Kaufman RJ. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell. 2001;7:1165–76.

    Article  CAS  PubMed  Google Scholar 

  • Schreier MH, Erni B, Staehelin T. Initiation of mammalian protein synthesis. I. Purification and characterization of seven initiation factors. J Mol Biol. 1977;116:727–53.

    Article  CAS  PubMed  Google Scholar 

  • Shafritz DA, Prichard PM, Gilbert JM, Anderson WF. Separation of two factors, M1 and M2, required for poly U dependent polypeptide synthesis by rabbit reticulocyte ribosomes at low magnesium ion concentration. Biochem Biophys Res Commun. 1970;38:721–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work in our group is funded by Breast Cancer Campaign grant (2010NovPR13), Health Research Board (grant number HRA-POR-2014-643), Belgium Grant (IAP 7/32), a Science Foundation Ireland (SFI) grant co-funded under the European Regional Development Fund (grant Number 13/RC/2073), and EU H2020 MSCA ITN-675448 (TRAINERS). K.M. is funded by an Irish Research Council Fellowship (grant number GOIPD/2014/53).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katarzyna Mnich .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Pakos-Zebrucka, K., Gorman, A.M., Chintha, C., Chevet, E., Samali, A., Mnich, K. (2016). EIF2S1. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101587-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_101587-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics