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Gene Review

EIF2S1  -  eukaryotic translation initiation factor 2...

Homo sapiens

Synonyms: EIF-2, EIF-2A, EIF-2alpha, EIF2, EIF2A, ...
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Disease relevance of EIF2S1


High impact information on EIF2S1

  • There is good evidence that a variety of viruses encode functions that inhibit activation of either ribonuclease L or the Pl/eIF-2 alpha kinase [6].
  • A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis [7].
  • In necrosis induced by tumor necrosis factor, double-stranded RNA, or viral infection, de novo protein synthesis persists and 28S ribosomal RNA fragmentation, eIF2-alpha phosphorylation, and proteolytic activation of PKR are absent [8].
  • The ability of a TIA-1 mutant lacking its RNA-binding domains to function as a transdominant inhibitor of SG formation suggests that this RNA-binding protein acts downstream of the phosphorylation of eIF-2alpha to promote the sequestration of untranslated mRNAs at SGs [9].
  • RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules [9].

Biological context of EIF2S1


Anatomical context of EIF2S1

  • Quiescent T cells expressed low levels of eIF-2 alpha, -4E, and -4A mRNAs and proteins as compared to proliferating T cells [12].
  • Furthermore, expression of a mutant form of eIF-2 alpha, which cannot be phosphorylated on Ser51 also caused malignant transformation of NIH 3T3 cells [14].
  • In response to various environmental stresses, eukaryotic cells down-regulate protein synthesis by phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2alpha) [5].
  • We report the identification and characterization of a cDNA from rat pancreatic islet cells that encodes a new related kinase, which we term pancreatic eIF-2alpha kinase, or PEK [5].
  • Recombinant pK3 prevents the inhibition of protein synthesis by dsRNA in a cell-free translation system from rabbit reticulocytes at levels equal to, or lower than, the level of endogenous eIF-2 alpha [15].

Associations of EIF2S1 with chemical compounds

  • GADD34 expression also reversed eIF-2 alpha phosphorylation induced by okadaic acid but not that induced by another phosphatase inhibitor, calyculin A (CA), which is a result consistent with PP1 being a component of the GADD34-assembled eIF-2 alpha phosphatase [10].
  • Eukaryotic translation initiation factor 2alpha (eIF-2alpha), a target molecule of the interferon-inducible double-stranded-RNA-dependent protein kinase (PKR), was cleaved in apoptotic Saos-2 cells on treatment with poly(I).poly(C) or tumour necrosis factor alpha [16].
  • However, bortezomib rapidly induced components of the proapoptotic/terminal UPR, including PERK, the ER stress-specific eIF-2alpha kinase; ATF4, an ER stress-induced transcription factor; and its proapoptotic target, CHOP/GADD153 [17].
  • Inhibition of protein synthesis correlates with eIF-2alpha phosphorylation in response to a wide variety of different stimuli, including heat shock, serum deprivation, glucose starvation, amino acid starvation, exposure to heavy metal ions, and viral infection [18].
  • Neither Co-eIF-2 alpha nor Co-eIF-2 beta enhances the rate of exchange between GDP bound to eIF-2 and free GDP, indicating that neither factor functions as a guanine nucleotide exchange factor [19].

Physical interactions of EIF2S1


Enzymatic interactions of EIF2S1

  • PKR phosphorylates eIF-2alpha on Ser(51), resulting in the suppression of protein synthesis [16].

Regulatory relationships of EIF2S1


Other interactions of EIF2S1


Analytical, diagnostic and therapeutic context of EIF2S1


  1. Herpes simplex virus 1 infection activates the endoplasmic reticulum resident kinase PERK and mediates eIF-2alpha dephosphorylation by the gamma(1)34.5 protein. Cheng, G., Feng, Z., He, B. J. Virol. (2005) [Pubmed]
  2. The cowpox virus host range gene, CP77, affects phosphorylation of eIF2 alpha and vaccinia viral translation in apoptotic HeLa cells. Hsiao, J.C., Chung, C.S., Drillien, R., Chang, W. Virology (2004) [Pubmed]
  3. Regulation of the cell-cycle-dependent internal ribosome entry site of the PITSLRE protein kinase: roles of Unr (upstream of N-ras) protein and phosphorylated translation initiation factor eIF-2alpha. Tinton, S.A., Schepens, B., Bruynooghe, Y., Beyaert, R., Cornelis, S. Biochem. J. (2005) [Pubmed]
  4. Protein synthesis and protein phosphorylation during heat stress, recovery, and adaptation. Duncan, R.F., Hershey, J.W. J. Cell Biol. (1989) [Pubmed]
  5. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Shi, Y., Vattem, K.M., Sood, R., An, J., Liang, J., Stramm, L., Wek, R.C. Mol. Cell. Biol. (1998) [Pubmed]
  6. Impact of virus infection on host cell protein synthesis. Schneider, R.J., Shenk, T. Annu. Rev. Biochem. (1987) [Pubmed]
  7. A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis. Mazeyrat, S., Saut, N., Grigoriev, V., Mahadevaiah, S.K., Ojarikre, O.A., Rattigan A, n.u.l.l., Bishop, C., Eicher, E.M., Mitchell, M.J., Burgoyne, P.S. Nat. Genet. (2001) [Pubmed]
  8. Protein synthesis persists during necrotic cell death. Saelens, X., Festjens, N., Parthoens, E., Vanoverberghe, I., Kalai, M., van Kuppeveld, F., Vandenabeele, P. J. Cell Biol. (2005) [Pubmed]
  9. RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. Kedersha, N.L., Gupta, M., Li, W., Miller, I., Anderson, P. J. Cell Biol. (1999) [Pubmed]
  10. Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Brush, M.H., Weiser, D.C., Shenolikar, S. Mol. Cell. Biol. (2003) [Pubmed]
  11. Translation inhibition in apoptosis: caspase-dependent PKR activation and eIF2-alpha phosphorylation. Saelens, X., Kalai, M., Vandenabeele, P. J. Biol. Chem. (2001) [Pubmed]
  12. Regulation of translation initiation factor gene expression during human T cell activation. Mao, X., Green, J.M., Safer, B., Lindsten, T., Frederickson, R.M., Miyamoto, S., Sonenberg, N., Thompson, C.B. J. Biol. Chem. (1992) [Pubmed]
  13. Regulation of gene expression for translation initiation factor eIF-2 alpha: importance of the 3' untranslated region. Miyamoto, S., Chiorini, J.A., Urcelay, E., Safer, B. Biochem. J. (1996) [Pubmed]
  14. Abrogation of translation initiation factor eIF-2 phosphorylation causes malignant transformation of NIH 3T3 cells. Donzé, O., Jagus, R., Koromilas, A.E., Hershey, J.W., Sonenberg, N. EMBO J. (1995) [Pubmed]
  15. Recombinant vaccinia virus K3L gene product prevents activation of double-stranded RNA-dependent, initiation factor 2 alpha-specific protein kinase. Carroll, K., Elroy-Stein, O., Moss, B., Jagus, R. J. Biol. Chem. (1993) [Pubmed]
  16. Caspase-mediated cleavage of eukaryotic translation initiation factor subunit 2alpha. Satoh, S., Hijikata, M., Handa, H., Shimotohno, K. Biochem. J. (1999) [Pubmed]
  17. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Obeng, E.A., Carlson, L.M., Gutman, D.M., Harrington, W.J., Lee, K.P., Boise, L.H. Blood (2006) [Pubmed]
  18. The eIF-2alpha kinases and the control of protein synthesis. de Haro, C., Méndez, R., Santoyo, J. FASEB J. (1996) [Pubmed]
  19. Factors from wheat germ that enhance the activity of eukaryotic initiation factor eIF-2. Isolation and characterization of Co-eIF-2 alpha. Osterhout, J.J., Lax, S.R., Ravel, J.M. J. Biol. Chem. (1983) [Pubmed]
  20. Stimulation of protein synthesis in COS cells transfected with variants of the alpha-subunit of initiation factor eIF-2. Choi, S.Y., Scherer, B.J., Schnier, J., Davies, M.V., Kaufman, R.J., Hershey, J.W. J. Biol. Chem. (1992) [Pubmed]
  21. Activation of the double-stranded-RNA-activated protein kinase and induction of vascular cell adhesion molecule-1 by poly (I).poly (C) in endothelial cells. Offermann, M.K., Zimring, J., Mellits, K.H., Hagan, M.K., Shaw, R., Medford, R.M., Mathews, M.B., Goodbourn, S., Jagus, R. Eur. J. Biochem. (1995) [Pubmed]
  22. Association of a M(r) 90,000 phosphoprotein with protein kinase PKR in cells exhibiting enhanced phosphorylation of translation initiation factor eIF-2 alpha and premature shutoff of protein synthesis after infection with gamma 134.5- mutants of herpes simplex virus 1. Chou, J., Chen, J.J., Gross, M., Roizman, B. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  23. A eukaryotic translation initiation factor 2-associated 67 kDa glycoprotein partially reverses protein synthesis inhibition by activated double-stranded RNA-dependent protein kinase in intact cells. Wu, S., Rehemtulla, A., Gupta, N.K., Kaufman, R.J. Biochemistry (1996) [Pubmed]
  24. Mechanical force activates eIF-2alpha phospho-kinases in fibroblast. Wang, J., Laschinger, C., Zhao, X.H., Mak, B., Seth, A., McCulloch, C.A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  25. Independent signaling of grp78 gene transcription and phosphorylation of eukaryotic initiator factor 2 alpha by the stressed endoplasmic reticulum. Brostrom, M.A., Prostko, C.R., Gmitter, D., Brostrom, C.O. J. Biol. Chem. (1995) [Pubmed]
  26. Eukaryotic methionyl aminopeptidases: two classes of cobalt-dependent enzymes. Arfin, S.M., Kendall, R.L., Hall, L., Weaver, L.H., Stewart, A.E., Matthews, B.W., Bradshaw, R.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  27. A difference in the rate of ribosomal elongation balances the synthesis of eukaryotic translation initiation factor (eIF)-2 alpha and eIF-2 beta. Chiorini, J.A., Boal, T.R., Miyamoto, S., Safer, B. J. Biol. Chem. (1993) [Pubmed]
  28. Regulation of initiation factors during translational repression caused by serum depletion. Covalent modification. Duncan, R., Hershey, J.W. J. Biol. Chem. (1985) [Pubmed]
  29. Expression of translation initiation factors elF-4E and elF-2alpha and a potential physiologic role of continuous protein synthesis in human platelets. Rosenwald, I.B., Pechet, L., Han, A., Lu, L., Pihan, G., Woda, B., Chen, J.J., Szymanski, I. Thromb. Haemost. (2001) [Pubmed]
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