Gene Symbol: Eif2s1
Description: eukaryotic translation initiation factor 2 subunit alpha
Alias: eukaryotic translation initiation factor 2 subunit 1, EIF-2A, EIF-2alpha, eIF-2-alpha, eukaryotic translation initiation factor 2 subunit 1 alpha
Species: rat
Products:     Eif2s1

Top Publications

  1. Chang G, Liu R, Panniers R, Li G. Rat fibroblasts transfected with the human 70-kDa heat shock gene exhibit altered translation and eukaryotic initiation factor 2 alpha phosphorylation following heat shock. Int J Hyperthermia. 1994;10:325-37 pubmed
    ..These results suggest that hsp70 may play a role in facilitating the dephosphorylation of eIF-2 alpha as well as reversing the inhibition of translation following heat shock. ..
  2. Vary T, Jurasinski C, Karinch A, Kimball S. Regulation of eukaryotic initiation factor-2 expression during sepsis. Am J Physiol. 1994;266:E193-201 pubmed
    ..Sterile inflammation or sepsis caused a 50% increase in the proportion of eIF-2 alpha mRNA associated with the polysomes compared with control.(ABSTRACT TRUNCATED AT 250 WORDS)..
  3. Petrov T, Underwood B, Braun B, Alousi S, Rafols J. Upregulation of iNOS expression and phosphorylation of eIF-2alpha are paralleled by suppression of protein synthesis in rat hypothalamus in a closed head trauma model. J Neurotrauma. 2001;18:799-812 pubmed
    ..Excessive amounts of NO may also participate in dysfunction of hypothalamic circuits that underlie endocrine and autonomic alterations following TBI. ..
  4. Ernst H, Duncan R, Hershey J. Cloning and sequencing of complementary DNAs encoding the alpha-subunit of translational initiation factor eIF-2. Characterization of the protein and its messenger RNA. J Biol Chem. 1987;262:1206-12 pubmed
    ..These results are consistent with the view that eIF-2 alpha mRNA translation is very efficient compared to other mRNAs in the cell. ..
  5. Hinnebusch A, Lorsch J. The mechanism of eukaryotic translation initiation: new insights and challenges. Cold Spring Harb Perspect Biol. 2012;4: pubmed publisher
    ..We also identify important unanswered questions that will require new ideas and techniques to solve. ..
  6. Unterberger U, Hoftberger R, Gelpi E, Flicker H, Budka H, Voigtlander T. Endoplasmic reticulum stress features are prominent in Alzheimer disease but not in prion diseases in vivo. J Neuropathol Exp Neurol. 2006;65:348-57 pubmed
    ..The lack of prominent activation of the PERK-eIF2alpha pathway in prion diseases suggests that, in contrast to AD, ER stress does not play a crucial role in neuronal death in prion disorders. ..
  7. Nakka V, Gusain A, Raghubir R. Endoplasmic reticulum stress plays critical role in brain damage after cerebral ischemia/reperfusion in rats. Neurotox Res. 2010;17:189-202 pubmed publisher
    ..Therefore, inhibition of ER stress following I/R injury may be used as key therapeutic target for neuroprotection. ..
  8. Sokka A, Putkonen N, Mudo G, Pryazhnikov E, Reijonen S, Khiroug L, et al. Endoplasmic reticulum stress inhibition protects against excitotoxic neuronal injury in the rat brain. J Neurosci. 2007;27:901-8 pubmed
    ..Inhibition of ER stress by small molecular compounds may be beneficial for treatment of various neuronal injuries and brain disorders. ..
  9. Cnop M, Ladriere L, Hekerman P, Ortis F, Cardozo A, Dogusan Z, et al. Selective inhibition of eukaryotic translation initiation factor 2 alpha dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis. J Biol Chem. 2007;282:3989-97 pubmed
    ..This modifies the present paradigm regarding the beneficial role of eIF2alpha phosphorylation in beta-cells and must be taken into consideration when designing therapies to protect beta-cells in type 2 diabetes. ..

More Information


  1. Hamanaka R, Bennett B, Cullinan S, Diehl J. PERK and GCN2 contribute to eIF2alpha phosphorylation and cell cycle arrest after activation of the unfolded protein response pathway. Mol Biol Cell. 2005;16:5493-501 pubmed
    ..Our results demonstrate that PERK and GCN2 function to cooperatively regulate eIF2alpha phosphorylation and cyclin D1 translation after UPR activation. ..
  2. Pereira C, Sattlegger E, Jiang H, Longo B, Jaqueta C, Hinnebusch A, et al. IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation. J Biol Chem. 2005;280:28316-23 pubmed
    ..These results suggest that IMPACT ensures constant high levels of translation and low levels of ATF4 and CHOP in specific neuronal cells under amino acid starvation conditions. ..
  3. Kimball S, Horetsky R, Ron D, Jefferson L, Harding H. Mammalian stress granules represent sites of accumulation of stalled translation initiation complexes. Am J Physiol Cell Physiol. 2003;284:C273-84 pubmed
    ..Finally, we also show that stress granules contain many, if not all, of the components of the 48S preinitiation complex, but not 60S ribosomal subunits, suggesting that they represent stalled translation initiation complexes. ..
  4. Mikami S, Masutani M, Sonenberg N, Yokoyama S, Imataka H. An efficient mammalian cell-free translation system supplemented with translation factors. Protein Expr Purif. 2006;46:348-57 pubmed
    ..Collectively, the translation factor-supplemented HeLa cell extract should become an important tool for the production of recombinant proteins. ..
  5. Gaccioli F, White V, Capobianco E, Powell T, Jawerbaum A, Jansson T. Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2alpha signaling and increases fetal growth in rats. Biol Reprod. 2013;89:96 pubmed publisher
    ..We speculate that these changes may up-regulate protein synthesis and contribute to placental and fetal overgrowth. ..
  6. Segev Y, Michaelson D, Rosenblum K. ApoE ?4 is associated with eIF2? phosphorylation and impaired learning in young mice. Neurobiol Aging. 2013;34:863-72 pubmed publisher
  7. Bommer U, Lutsch G, Behlke J, Stahl J, Nesytova N, Henske A, et al. Shape and location of eukaryotic initiation factor eIF-2 on the 40S ribosomal subunit of rat liver. Immunoelectron-microscopic and hydrodynamic investigations. Eur J Biochem. 1988;172:653-62 pubmed
    ..5. This conclusion is further confirmed by a calculated frictional ratio of 1.37 and a Stokes radius of about 4.54 nm. ..
  8. Kimball S, Fabian J, Pavitt G, Hinnebusch A, Jefferson L. Regulation of guanine nucleotide exchange through phosphorylation of eukaryotic initiation factor eIF2alpha. Role of the alpha- and delta-subunits of eiF2b. J Biol Chem. 1998;273:12841-5 pubmed
    ..The results provide the first direct biochemical evidence that the alpha- and delta-subunits of eIF2B are involved in mediating the effect of substrate phosphorylation. ..
  9. Harding H, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell. 2000;6:1099-108 pubmed
    ..Mammalian cells thus utilize an ancient pathway to regulate gene expression in response to diverse stress signals. ..
  10. Jian M, Luo Y, Xue Y, Han Y, Shi H, Liu J, et al. eIF2? dephosphorylation in basolateral amygdala mediates reconsolidation of drug memory. J Neurosci. 2014;34:10010-21 pubmed publisher
    ..These results demonstrate that eIF2? dephosphorylation in the BLA mediates the memory reconsolidation of drug-paired stimuli. ..
  11. Bommer U, Stahl J, Henske A, Lutsch G, Bielka H. Identification of proteins of the 40 S ribosomal subunit involved in interaction with initiation factor eIF-2 in the quaternary initiation complex by means of monospecific antibodies. FEBS Lett. 1988;233:114-8 pubmed
    ..Therefore, from the ribosomal proteins tested, only proteins S3a, S13/16, S19 and S24 are concluded to be involved in eIF-2 binding to the 40 S subunit. ..
  12. Lourenco M, Clarke J, Frozza R, Bomfim T, Forny Germano L, Batista A, et al. TNF-? mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer's ?-amyloid oligomers in mice and monkeys. Cell Metab. 2013;18:831-43 pubmed publisher
    ..Results reveal pathogenic mechanisms shared by AD and diabetes and establish that proinflammatory signaling mediates oligomer-induced IRS-1 inhibition and PKR-dependent synapse and memory loss...
  13. Wu C, Liu R, Gao M, Zhao G, Wu S, Wu C, et al. Pinocembrin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress induced apoptosis. Neurosci Lett. 2013;546:57-62 pubmed publisher
    ..These results suggest that the attenuation of ER stress induced apoptosis may be involved in the mechanisms of pinocembrin...
  14. Colbert R, Hucul J, Scorsone K, Young D. Alpha subunit of eukaryotic translational initiation factor-2 is a heat-shock protein. J Biol Chem. 1987;262:16763-6 pubmed
    ..In addition to identifying a function for one of the heat-shock proteins, our findings draw attention to the likelihood that other low-abundance heat-shock proteins may play critical roles in the heat-shock response. ..
  15. Paccalin M, Pain Barc S, Pluchon C, Paul C, Besson M, Carret Rebillat A, et al. Activated mTOR and PKR kinases in lymphocytes correlate with memory and cognitive decline in Alzheimer's disease. Dement Geriatr Cogn Disord. 2006;22:320-6 pubmed
    ..These results suggest that the levels of mTOR, PKR and eIF2alpha in lymphocytes could follow the cognitive decline in AD. ..
  16. Wang A, Li X, Yang Y, Li W, Zhang W, Hu C, et al. A Critical Role of the mTOR/eIF2α Pathway in Hypoxia-Induced Pulmonary Hypertension. PLoS ONE. 2015;10:e0130806 pubmed publisher
    ..These results suggest a critical role of the mTOR/eIF2αpathway in hypoxic vascular remodeling and PASMCs proliferation of HPH. ..
  17. Hinnebusch A. The scanning mechanism of eukaryotic translation initiation. Annu Rev Biochem. 2014;83:779-812 pubmed publisher
    ..A second GTPase, eIF5B, catalyzes the joining of the 60S subunit to produce an 80S initiation complex that is competent for elongation...
  18. Paytubi S, Morrice N, Boudeau J, Proud C. The N-terminal region of ABC50 interacts with eukaryotic initiation factor eIF2 and is a target for regulatory phosphorylation by CK2. Biochem J. 2008;409:223-31 pubmed
    ..Expression of a mutant of ABC50 in which both sites are mutated to alanine markedly decreased the association of eIF2 with 80S ribosomal and polysomal fractions...
  19. Borck G, Shin B, Stiller B, Mimouni Bloch A, Thiele H, Kim J, et al. eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation. Mol Cell. 2012;48:641-6 pubmed publisher
    ..These findings directly link intellectual disability to impaired translation initiation, and provide a mechanistic basis for the human disease due to partial loss of eIF2 function. ..
  20. Yamaji M, Tanaka T, Shigeta M, Chuma S, Saga Y, Saitou M. Functional reconstruction of NANOS3 expression in the germ cell lineage by a novel transgenic reporter reveals distinct subcellular localizations of NANOS3. Reproduction. 2010;139:381-93 pubmed publisher
    ..These findings unveil the presence of distinct posttranscriptional regulations in PGCs soon after their specification, for which RNA-binding proteins such as NANOS3 and TIAL1 would play critical functions. ..
  21. Althausen S, Mengesdorf T, Mies G, Olah L, Nairn A, Proud C, et al. Changes in the phosphorylation of initiation factor eIF-2alpha, elongation factor eEF-2 and p70 S6 kinase after transient focal cerebral ischaemia in mice. J Neurochem. 2001;78:779-87 pubmed
  22. Montie H, Kayali F, Haezebrouck A, Rossi N, DeGracia D. Renal ischemia and reperfusion activates the eIF 2 alpha kinase PERK. Biochim Biophys Acta. 2005;1741:314-24 pubmed
    ..inhibits translation initiation via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF 2 alpha, phospho-form eIF 2 alpha(P)]...
  23. Chen Y, Chen G, Fan Z, Luo J, Ke Z. GSK3beta and endoplasmic reticulum stress mediate rotenone-induced death of SK-N-MC neuroblastoma cells. Biochem Pharmacol. 2008;76:128-38 pubmed publisher
    ..Taken together, the results suggest that GSK3beta activation and ER stress contribute separately to rotenone cytotoxicity. ..
  24. Han X, Wang J, Wang L, Zheng P, Ji G. [Role of PERK/eIF2a signaling pathway in hepatocyte apoptosis of alcoholic liver injury rats]. Zhonghua Gan Zang Bing Za Zhi. 2010;18:768-72 pubmed publisher
  25. Burda J, Martin M, Garcia A, Alcazar A, Fando J, Salinas M. Phosphorylation of the alpha subunit of initiation factor 2 correlates with the inhibition of translation following transient cerebral ischaemia in the rat. Biochem J. 1994;302 ( Pt 2):335-8 pubmed
    ..Moreover, GEF activity measured in the GDP-exchange assay was in fact inhibited in the ischaemic animals, proving that protein synthesis is impaired by the presence of eIF-2(alpha P), which blocks eIF-2 recycling. ..
  26. Xue B, Fitzgerald C, Jin D, Mao L, Wang J. Amphetamine elevates phosphorylation of eukaryotic initiation factor 2? (eIF2?) in the rat forebrain via activating dopamine D1 and D2 receptors. Brain Res. 2016;1646:459-466 pubmed publisher
    ..These results demonstrate the sensitivity of eIF2? to stimulant exposure. AMPH possesses the ability to stimulate eIF2? phosphorylation in striatal and mPFC neurons in vivo in a D1 and D2 receptor-dependent manner. ..
  27. Williams D, Price N, Loughlin A, Proud C. Characterization of the mammalian initiation factor eIF2B complex as a GDP dissociation stimulator protein. J Biol Chem. 2001;276:24697-703 pubmed
    ..Supplementation of such preparations with recombinant eIF2Balpha markedly enhances activity, indicating that eIF2Balpha is required for full activity of mammalian eIF2B. ..
  28. Deng J, Harding H, Raught B, Gingras A, Berlanga J, Scheuner D, et al. Activation of GCN2 in UV-irradiated cells inhibits translation. Curr Biol. 2002;12:1279-86 pubmed
    ..These results provide a mechanism for translation inhibition by UV irradiation and identify a hitherto unrecognized role for mammalian GCN2 as a mediator of the cellular response to UV stress. ..
  29. Kimball S, O Malley J, Anthony J, Crozier S, Jefferson L. Assessment of biomarkers of protein anabolism in skeletal muscle during the life span of the rat: sarcopenia despite elevated protein synthesis. Am J Physiol Endocrinol Metab. 2004;287:E772-80 pubmed
    ..The results are consistent with a model wherein protein synthesis is enhanced during aging in a futile attempt to maintain muscle mass. ..
  30. Xu B, Wang F, Wu S, Deng Y, Liu W, Feng S, et al. ?-Synuclein is involved in manganese-induced ER stress via PERK signal pathway in organotypic brain slice cultures. Mol Neurobiol. 2014;49:399-412 pubmed publisher
    ..Moreover, alpha-synuclein protein was associated with Mn-induced activation of PERK signaling pathway. ..
  31. Harding H, Zhang Y, Bertolotti A, Zeng H, Ron D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell. 2000;5:897-904 pubmed
    ..PERK thus plays a major role in the ability of cells to adapt to ER stress. ..
  32. Hussain S, Ramaiah K. Reduced eIF2alpha phosphorylation and increased proapoptotic proteins in aging. Biochem Biophys Res Commun. 2007;355:365-70 pubmed
  33. Goldstein E, Owen C, White B, Rafols J. Ultrastructural localization of phosphorylated eIF2alpha [eIF2alpha(P)] in rat dorsal hippocampus during reperfusion. Acta Neuropathol. 1999;98:493-505 pubmed
    ..The beta-subunit of eIF2 has a zinc finger and polylysine blocks analogous to those on other proteins that affect transcription. The association of eIF2alpha(P) with chromatin may have important implications for transcription. ..
  34. DeGracia D, Sullivan J, Neumar R, Alousi S, Hikade K, Pittman J, et al. Effect of brain ischemia and reperfusion on the localization of phosphorylated eukaryotic initiation factor 2 alpha. J Cereb Blood Flow Metab. 1997;17:1291-302 pubmed
    ..These observations, together with the fact that eIF-2(alpha P) inhibits translation initiation, make a compelling case that eIF-2(alpha P) is responsible for reperfusion-induced inhibition of protein synthesis in vulnerable neurons. ..