Gene Symbol: EIF2A
Description: eukaryotic translation initiation factor 2A
Alias: CDA02, EIF-2A, MST089, MSTP004, MSTP089, eukaryotic translation initiation factor 2A, 65 kDa eukaryotic translation initiation factor 2A, eukaryotic translation initiation factor 2A, 65kDa
Species: human
Products:     EIF2A

Top Publications

  1. 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 pubmed
    ..It further indicates a previously unrecognized evolutionary lineage of eIF2alpha/gamma from the functionally related elongation factor eEF1Balpha/eEF1A complex. ..
  2. Schewe D, Aguirre Ghiso J. Inhibition of eIF2alpha dephosphorylation maximizes bortezomib efficiency and eliminates quiescent multiple myeloma cells surviving proteasome inhibitor therapy. Cancer Res. 2009;69:1545-52 pubmed publisher
    ..Thus, strategies that maintain eIF2alpha in a hyperphosphorylated state may be a novel therapeutic approach to maximize bortezomib-induced apoptosis and reduce residual disease and recurrences in this type of cancer. ..
  3. Bae G, Park E, Baek D, Jun H, Oh Y. Liquiritigenin prevents palmitate-induced beta-cell apoptosis via estrogen receptor-mediated AKT activation. Biomed Pharmacother. 2018;101:348-354 pubmed publisher
    ..We conclude that estrogen receptor-mediated AKT phosphorylation is one of the mechanisms contributing to the anti-apoptotic effect of LQ. ..
  4. Lu W, László C, Miao Z, Chen H, Wu S. The role of nitric-oxide synthase in the regulation of UVB light-induced phosphorylation of the alpha subunit of eukaryotic initiation factor 2. J Biol Chem. 2009;284:24281-8 pubmed publisher
    ..The results presented above led us to propose that NOS mediates UV-induced eIF2alpha phosphorylation by activation of both PERK and GCN2 via oxidative stress and l-arginine starvation signaling pathways. ..
  5. Wang Z, Qi J, Liu L, Li J, Xu H, Liang B, et al. Valsartan reduces AT1-AA-induced apoptosis through suppression oxidative stress mediated ER stress in endothelial progenitor cells. Eur Rev Med Pharmacol Sci. 2017;21:1159-1168 pubmed
    ..Valsartan could inhibit AT1-AA-induced apoptosis through inhibiting oxidative stress mediated ER stress in EPCs. ..
  6. Lu Y, Xu J, Zhang X, Zhao X. Gu-Ben-Fang-Xiao decoction attenuates sustained airway inflammation by suppressing ER stress response in a murine asthma remission model of respiratory syncytial virus infection. J Ethnopharmacol. 2016;192:496-509 pubmed publisher
    ..levels of asthma susceptibility gene ORMDL3, ER stress markers (BIP, CHOP), and three canonical UPR branches (PERK-eIF2a-ATF4, IRE1?-XBP1/IRE1?-JNK-AP1 and ATF6-SERCA2b signal pathways) were detected using real-time RT-PCR and western ..
  7. Cubi R, Vembar S, Biton A, Franetich J, Bordessoulles M, Sossau D, et al. Laser capture microdissection enables transcriptomic analysis of dividing and quiescent liver stages of Plasmodium relapsing species. Cell Microbiol. 2017;19: pubmed publisher
    ..cynomolgi and P. vivax, and the global translational repressor, eIF2a kinase eIK2, all of which are upregulated in the hypnozoite...
  8. Zhang J, Cao J, Weng Q, Wu R, Yan Y, Jing H, et al. Suppression of hypoxia-inducible factor 1? (HIF-1?) by tirapazamine is dependent on eIF2? phosphorylation rather than the mTORC1/4E-BP1 pathway. PLoS ONE. 2010;5:e13910 pubmed publisher
    ..In conclusion, our findings suggest that TPZ is a potent regulator of HIF-1? and provide new insight into the potential molecular mechanism whereby TPZ serves to reduce HIF-1? expression. ..
  9. Nayak R, Pintel D. Adeno-associated viruses can induce phosphorylation of eIF2alpha via PKR activation, which can be overcome by helper adenovirus type 5 virus-associated RNA. J Virol. 2007;81:11908-16 pubmed

More Information

Publications122 found, 100 shown here

  1. Lees E, Krol E, Grant L, Shearer K, Wyse C, Moncur E, et al. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21. Aging Cell. 2014;13:817-27 pubmed publisher
    ..of methionine exhibited increased circulating and hepatic gene expression levels of FGF21, phosphorylation of eIF2a, and expression of ATF4, with a concomitant decrease in IRE1? phosphorylation...
  2. Koumenis C, Naczki C, Koritzinsky M, Rastani S, Diehl A, Sonenberg N, et al. 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 pubmed
  3. Friend K, Brooks H, Propson N, Thomson J, Kimble J. Embryonic Stem Cell Growth Factors Regulate eIF2α Phosphorylation. PLoS ONE. 2015;10:e0139076 pubmed publisher
    ..These experiments connect ESC growth factors to eIF2α phosphorylation and suggest a chemical substitute for LIF to enhance Nanog and c-Myc expression. ..
  4. Lenox A, Bhootada Y, Gorbatyuk O, FULLARD R, Gorbatyuk M. Unfolded protein response is activated in aged retinas. Neurosci Lett. 2015;609:30-5 pubmed publisher
    ..Using western blotting, we determined that the hallmarks of the UPR PERK arm, phosphorylated (p) eIF2a, ATF4, and GADD34, were significantly altered in aged vs. young rat retinas...
  5. Cao S, Yan B, Lu Y, Zhang G, Li J, Guo W, et al. C/EBP homologous protein-mediated endoplasmic reticulum stress-related renal apoptosis is involved in rats with brain death. Transplant Proc. 2015;47:354-8 pubmed publisher
    ..Salubrinal (Sal) significantly increased levels of p-eIF2a and decreased the activity of CHOP at 6 hours after BD compared with vehicle-treated dimethylsulfoxide...
  6. Xu T, Alharthi A, Batistel F, Helmbrecht A, Parys C, Trevisi E, et al. Hepatic phosphorylation status of serine/threonine kinase 1, mammalian target of rapamycin signaling proteins, and growth rate in Holstein heifer calves in response to maternal supply of methionine. J Dairy Sci. 2018;101:8476-8491 pubmed publisher
    ..supply, there were overall decreases in phosphorylation ratios of AKT, MTOR, RPS6KB1, and eukaryotic translation initiation factor 2A (EIF2A) over time...
  7. Ni X, Lu W, Zhang J, Zhu Q, Ren J, Yu Y, et al. Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice. Endocrine. 2018;62:90-106 pubmed publisher
    ..AngII-treated mouse aortas showed increased ERS gene transcription of caspase12, eukaryotic translation initiation factor 2a (eIf2a) and activating transcription factor 4(ATF4)...
  8. Sendoel A, Dunn J, Rodriguez E, Naik S, Gomez N, Hurwitz B, et al. Translation from unconventional 5' start sites drives tumour initiation. Nature. 2017;541:494-499 pubmed publisher
    ..Conversely, the alternative initiation factor eIF2A is essential for cancer progression, during which it mediates initiation at these upstream sites, differentially ..
  9. Liu A, Pang C, Liu G, Wang S, Chu C, Li L, et al. Ameliorative effect of sevoflurane on endoplasmic reticulum stress mediates cardioprotection against ischemic/reperfusion injury. Can J Physiol Pharmacol. 2018;: pubmed publisher
    ..results suggest that the cardioprotection of sevoflurane against IR injury might be mediated by suppressing PERK/eIF2a/ATF4/CHOP signaling via activating the Akt pathway, which helps in understanding the novel mechanism of the ..
  10. Sanz M, González Almela E, Carrasco L. Translation of Sindbis Subgenomic mRNA is Independent of eIF2, eIF2A and eIF2D. Sci Rep. 2017;7:43876 pubmed publisher
    ..Several studies have suggested that eIF2 can be replaced by eIF2A or eIF2D...
  11. Kloft N, Neukirch C, von Hoven G, Bobkiewicz W, Weis S, Boller K, et al. A subunit of eukaryotic translation initiation factor 2?-phosphatase (CreP/PPP1R15B) regulates membrane traffic. J Biol Chem. 2012;287:35299-317 pubmed publisher
    ..CReP was also required for exocytosis from erythroleukemia cells and thus appears to play a broader role in membrane traffic. In summary, the mammalian traffic machinery co-opts p-eIF2? and CReP, regulators of translation initiation. ..
  12. Borkham Kamphorst E, Steffen B, Van De Leur E, Haas U, Tihaa L, Friedman S, et al. CCN1/CYR61 overexpression in hepatic stellate cells induces ER stress-related apoptosis. Cell Signal. 2016;28:34-42 pubmed publisher
    ..The UPR arm PERK and eIF2a was phosphorylated, combined with significant CHOP upregulation...
  13. Burger J, Landau D, Taylor Weiner A, Bozic I, Zhang H, Sarosiek K, et al. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition. Nat Commun. 2016;7:11589 pubmed publisher
    ..three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma...
  14. Ebersbach Silva P, Poletto A, David Silva A, Seraphim P, Anhê G, Passarelli M, et al. Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement. Lipids Health Dis. 2018;17:64 pubmed publisher
    ..These results link ER stress, inflammation and insulin resistance in L6 cells. ..
  15. Song Q, Han C, Xiong X, He F, Gan W, Wei S, et al. PI3K-Akt-mTOR signal inhibition affects expression of genes related to endoplasmic reticulum stress. Genet Mol Res. 2016;15: pubmed publisher
    ..Thereafter, the expression levels of genes involved in the ER stress (BIP, EIF2a, ATF6, and XBP1) were assessed. The results indicated that the mRNA level of BIP was up-regulated in 0...
  16. Li X, Liu C, Ip B, Hu K, Smith D, Greenberg A, et al. Tumor progression locus 2 ablation suppressed hepatocellular carcinoma development by inhibiting hepatic inflammation and steatosis in mice. J Exp Clin Cancer Res. 2015;34:138 pubmed publisher
    ..The study revealed for the first time that Tpl2 plays a significant role in promoting HCC development by its pro-inflammatory effect, which suggested that Tpl2 could be a molecular target for HCC prevention. ..
  17. Caballero Molada M, Planes M, Benlloch H, Atares S, Naranjo M, Serrano R. The Gcn2-eIF2α pathway connects iron and amino acid homeostasis in Saccharomyces cerevisiae. Biochem J. 2018;475:1523-1534 pubmed publisher
    ..This mechanism adjusts the uptake of iron to the needs of amino acid biosynthesis and expands the list of Gcn4-independent activities of the Gcn2-eIF2α regulatory system. ..
  18. Chen R, Rato C, Yan Y, Crespillo Casado A, Clarke H, Harding H, et al. G-actin provides substrate-specificity to eukaryotic initiation factor 2α holophosphatases. elife. 2015;4: pubmed publisher
    Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP...
  19. Kim E, Kim J, Seo K, Hong K, An S, Kwon J, et al. eIF2A, an initiator tRNA carrier refractory to eIF2? kinases, functions synergistically with eIF5B. Cell Mol Life Sci. 2018;: pubmed publisher
    ..The stress-resistant initiator tRNA carrier, eIF2A, was recently uncovered and shown to load Met-tRNA iMet on the 40S ribosomal subunit ..
  20. Wang Q, Duan L, Xu Z, Wang J, Xi S. The protective effect of the earthworm active ingredients on hepatocellular injury induced by endoplasmic reticulum stress. Biomed Pharmacother. 2016;82:304-11 pubmed publisher
    ..proteins, including PERK (protein kinase RNA-like endoplasmic reticulum kinase), eIF2a (eukaryotic translation initiation factor 2a), ATF4 (activating transcription factor 4) and CHOP (CCAAT/enhancer binding protein homologous ..
  21. Dong G, Liu Y, Zhang L, Huang S, Ding H, Dong Z. mTOR contributes to ER stress and associated apoptosis in renal tubular cells. Am J Physiol Renal Physiol. 2015;308:F267-74 pubmed publisher
    ..Inhibition of mTOR with rapamycin partially suppressed the phosphorylation of PERK and eIF2a and the induction of CHOP and GRP78 induction during tunicamycin treatment...
  22. Du L, He F, Kuang L, Tang W, Li Y, Chen D. eNOS/iNOS and endoplasmic reticulum stress-induced apoptosis in the placentas of patients with preeclampsia. J Hum Hypertens. 2017;31:49-55 pubmed publisher
    ..Placental protein expression of ER stress-related markers, including GRP78, GRP94, p-PERK, eIF2a, p-eIF2a, XBP1, CHOP, Ire1, p-Ire1 and iNOS, was higher, and eNOS expression was lower in PE (P<0...
  23. Squatrito M, Mancino M, Sala L, Draetta G. Ebp1 is a dsRNA-binding protein associated with ribosomes that modulates eIF2alpha phosphorylation. Biochem Biophys Res Commun. 2006;344:859-68 pubmed
    ..Our results demonstrate that Ebp1 is a new dsRNA-binding protein that acts as a cellular inhibitor of eIF2alpha phosphorylation suggesting that it could be involved in protein translation control. ..
  24. Leclerc G, Zheng S, Leclerc G, DeSalvo J, Swords R, Barredo J. The NEDD8-activating enzyme inhibitor pevonedistat activates the eIF2α and mTOR pathways inducing UPR-mediated cell death in acute lymphoblastic leukemia. Leuk Res. 2016;50:1-10 pubmed publisher
    ..Mechanistically, pevonedistat led to P-eIF2a dephosphorylation causing atypical proteotoxic/ER stress from failure to halt protein translation via the UPR and ..
  25. Sonobe Y, Ghadge G, Masaki K, Sendoel A, Fuchs E, Roos R. Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress. Neurobiol Dis. 2018;: pubmed publisher
    ..CRISPR/Cas9-induced knockout of a non-canonical translation initiation factor, eIF2A, impaired GA translation...
  26. Chu L, Vijay C, Annex B, Bader J, Popel A. PADPIN: protein-protein interaction networks of angiogenesis, arteriogenesis, and inflammation in peripheral arterial disease. Physiol Genomics. 2015;47:331-43 pubmed publisher
    ..several genes that are differentially expressed between the two mouse strains with known functions in PAD including TLR4, THBS1, and PRKAA2 and several genes with unknown functions in PAD including EphA4, TSPAN7, SLC22A4, and EIF2a.
  27. Li R, Zhou P, Guo Y, Lee J, Zhou B. Tris (1,3-dichloro-2-propyl) phosphate-induced apoptotic signaling pathways in SH-SY5Y neuroblastoma cells. Neurotoxicology. 2017;58:1-10 pubmed publisher
    ..TDCIPP led to the activation of protein markers of endoplasmic reticulum (ER) stress, including eukaryotic translation initiation factor 2a subunit (p-EIF2a), activation transcription factor (ATF4), glucose-regulated protein (GRP78), ..
  28. Dekervel J, Bulle A, Windmolders P, Lambrechts D, Van Cutsem E, Verslype C, et al. Acriflavine Inhibits Acquired Drug Resistance by Blocking the Epithelial-to-Mesenchymal Transition and the Unfolded Protein Response. Transl Oncol. 2017;10:59-69 pubmed publisher
    ..We showed that acriflavine blocked eIF2a phosphorylation and reduced ATF4 translation thereby inhibiting the PERK/eIF2a/ATF4 UPR pathway...
  29. Pan S, Jia Y, Yang X, Cai D, Liu Z, Song H, et al. Amino acid starvation-induced autophagy is involved in reduced subcutaneous fat deposition in weaning piglets derived from sows fed low-protein diet during gestation and lactation : Autophagy is involved in reduced fat deposition in maternal low-prot. Eur J Nutr. 2018;57:991-1001 pubmed publisher
  30. Gabr A, Lee H, Onphachanh X, Jung Y, Kim J, Chae C, et al. Ethanol-induced PGE2 up-regulates A? production through PKA/CREB signaling pathway. Biochim Biophys Acta Mol Basis Dis. 2017;1863:2942-2953 pubmed publisher
    ..By using salubrinal (an eIF2? dephosphorylation inhibitor) or EIF2A siRNA, we found that eIF2? phosphorylation mediated the ethanol-induced COX-2 expression...
  31. Guo H, Cui H, Peng X, Fang J, Zuo Z, Deng J, et al. Nickel chloride (NiCl2) induces endoplasmic reticulum (ER) stress by activating UPR pathways in the kidney of broiler chickens. Oncotarget. 2016;7:17508-19 pubmed publisher
    ..Firstly, the PERK pathway was activated by increasing eIF2a and ATF4 mRNA expression...
  32. Liu Y, Qi S, Ru L, Ding C, Wang H, Li A, et al. [Salubrinal improves cardiac function in rats with heart failure post myocardial infarction through reducing endoplasmic reticulum stress-associated apoptosis]. Zhonghua Xin Xue Guan Bing Za Zhi. 2016;44:494-500 pubmed publisher
    ..The aim of the current study is to investigate the effects of salubrinal (Sal), a selective eIF2a dephosphorylation inhibitor, on heart failure rats and related mechanisms...
  33. Sharon E, Frenkel N. Human Herpesvirus 6A Exhibits Restrictive Propagation with Limited Activation of the Protein Kinase R-eIF2α Stress Pathway. J Virol. 2017;91: pubmed publisher
    ..Many viruses have evolved gene products targeting the PKR-eIF2a pathway, indicating its importance in antiviral defense...
  34. Bretin A, Carrière J, Dalmasso G, Bergougnoux A, B chir W, Maurin A, et al. Activation of the EIF2AK4-EIF2A/eIF2?-ATF4 pathway triggers autophagy response to Crohn disease-associated adherent-invasive Escherichia coli infection. Autophagy. 2016;12:770-83 pubmed publisher
    ..The underlying mechanism, however, remains unknown. Here, we investigated the role of the EIF2AK4-EIF2A/eIF2?-ATF4 pathway in the autophagic response to AIEC infection...
  35. Sanchez Martin M, Ambesi Impiombato A, Qin Y, Herranz D, Bansal M, Girardi T, et al. Synergistic antileukemic therapies in NOTCH1-induced T-ALL. Proc Natl Acad Sci U S A. 2017;114:2006-2011 pubmed publisher
    ..Mechanistically, network perturbation analyses showed eIF2A-phosphorylation-mediated inhibition of protein translation as a critical mediator of the antileukemic effects of ..
  36. Cormerais Y, Massard P, Vucetic M, Giuliano S, Tambutté E, Durivault J, et al. The glutamine transporter ASCT2 (SLC1A5) promotes tumor growth independently of the amino acid transporter LAT1 (SLC7A5). J Biol Chem. 2018;293:2877-2887 pubmed publisher
    ..i>LAT1KO cells, ASCT2KO cells displayed no amino acid (AA) stress response (GCN2/EIF2a/ATF4) or altered mTORC1 activity (S6K1/S6)...
  37. González Almela E, Williams H, Sanz M, Carrasco L. The Initiation Factors eIF2, eIF2A, eIF2D, eIF4A, and eIF4G Are Not Involved in Translation Driven by Hepatitis C Virus IRES in Human Cells. Front Microbiol. 2018;9:207 pubmed publisher
    ..Human HAP1 cells depleted for eIF2A, eIF2D, or both factors, were able to synthesize luciferase from an mRNA bearing the HCV IRES even when eIF2α ..
  38. Yerlikaya A, DoKudur H. Investigation of the eIF2alpha phosphorylation mechanism in response to proteasome inhibition in melanoma and breast cancer cells. Mol Biol (Mosk). 2010;44:859-66 pubmed
  39. Klein B, Tamir H, Hirschberg D, Ludwig R, Glickstein S, Myers M, et al. Oxytocin opposes effects of bacterial endotoxin on ER-stress signaling in Caco2BB gut cells. Biochim Biophys Acta. 2016;1860:402-11 pubmed publisher
    ..OT inactivates eukaryotic translation initiation factor 2a (eIF2a) without significant activation of protein kinase RNA-like endoplasmic reticulum kinase (..
  40. Teoh P, Bi C, Sintosebastian C, Tay L, Fonseca R, Chng W. PRIMA-1 targets the vulnerability of multiple myeloma of deregulated protein homeostasis through the perturbation of ER stress via p73 demethylation. Oncotarget. 2016;7:61806-61819 pubmed publisher
    ..Furthermore, there was a global attenuation of protein synthesis, correlated with phospho-eIF2a up-regulation...
  41. Amici D, Pinal Fernández I, Mázala D, Lloyd T, Corse A, Christopher Stine L, et al. Calcium dysregulation, functional calpainopathy, and endoplasmic reticulum stress in sporadic inclusion body myositis. Acta Neuropathol Commun. 2017;5:24 pubmed publisher
    ..of a Ca2+-activated protease, calpain-1, as well as increased signaling for translational attenuation (eIF2a phosphorylation) downstream of the unfolded protein response...
  42. Roy S, Esmaeilniakooshkghazi A, Patnaik S, Wang Y, George S, Ahrorov A, et al. Villin-1 and Gelsolin Regulate Changes in Actin Dynamics That Affect Cell Survival Signaling Pathways and Intestinal Inflammation. Gastroenterology. 2018;154:1405-1420.e2 pubmed publisher
    ..pathways result in phosphorylation of the eukaryotic translation initiation factor 2 subunit alpha (EIF2S1 or EIF2A), which affects regulation of protein translation...
  43. Luís A, Martins J, Silva A, Ferreira I, Cruz M, Neves B. Oxidative stress-dependent activation of the eIF2α–ATF4 unfolded protein response branch by skin sensitizer 1-fluoro-2,4-dinitrobenzene modulates dendritic-like cell maturation and inflammatory status in a biphasic manner [corrected]. Free Radic Biol Med. 2014;77:217-29 pubmed publisher
  44. You L, Shou J, Deng D, Jiang L, Jing Z, Yao J, et al. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines. Oncotarget. 2015;6:40268-82 pubmed publisher
    ..Firstly it inhibited cytoplasmic STAT3, which leads to the phosphorylation of EIF2A, then inhibited nuclear STAT3, which leads to the downregulation of BCL-2...
  45. Wen L, Han F, Shi Y, Li X. Role of the Endoplasmic Reticulum Pathway in the Medial Prefrontal Cortex in Post-Traumatic Stress Disorder Model Rats. J Mol Neurosci. 2016;59:471-82 pubmed publisher
    ..levels of three branch signalling pathways of ER: phosphorylated PERK (p-PERK)/phosphorylated eukaryotic translation initiation factor 2A (p-eIF2a), ATF6a/X-box binding protein 1 (XBP1), and IRE1a...
  46. Bruch J, Xu H, Rösler T, de Andrade A, Kuhn P, Lichtenthaler S, et al. PERK activation mitigates tau pathology in vitro and in vivo. EMBO Mol Med. 2017;9:371-384 pubmed publisher
    ..Importantly, the PERK substrate EIF2A, mediating some detrimental effects of PERK signaling, was downregulated in PSP brains and tauopathy models, ..
  47. Klein B, Tamir H, Ludwig R, Glickstein S, Welch M. Colostrum oxytocin modulates cellular stress response, inflammation, and autophagy markers in newborn rat gut villi. Biochem Biophys Res Commun. 2017;487:47-53 pubmed publisher
    ..villi primed and unprimed by colostrum by measuring levels of stress markers including BiP (an ER chaperone), eIF2a (translation initiation factor), and pPKR (eIF2a kinase)...
  48. Starck S, Tsai J, Chen K, Shodiya M, Wang L, Yahiro K, et al. Translation from the 5' untranslated region shapes the integrated stress response. Science. 2016;351:aad3867 pubmed publisher
    ..BiP expression during the ISR required both the alternative initiation factor eIF2A and non-AUG-initiated uORFs...
  49. Golovko A, Kojukhov A, Guan B, Morpurgo B, Merrick W, Mazumder B, et al. The eIF2A knockout mouse. Cell Cycle. 2016;15:3115-3120 pubmed
    Eukaryotic initiation factor 2A (eIF2A) is a 65-kDa protein that was first identified in the early 1970s as a factor capable of stimulating initiator methionyl-tRNAi (Met-tRNAMeti) binding to 40S ribosomal subunits ..
  50. Ren J, Seth P, Ye H, Guo K, Hanai J, Husain Z, et al. Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway. Sci Rep. 2017;7:4537 pubmed publisher
    ..suggested that citrate treatment inhibited AKT phosphorylation, activated PTEN and increased expression of p-eIF2a. We also found that p-eIF2a was decreased when PTEN was depleted...
  51. Su Q, Wang S, Baltzis D, Qu L, Wong A, Koromilas A. Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2alpha RNA-dependent protein kinase. Proc Natl Acad Sci U S A. 2006;103:63-8 pubmed
    ..Our data demonstrate an important role of tyrosine phosphorylation in biochemical and biological processes caused or mediated by the activation of the eIF2alpha kinase PKR. ..
  52. 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...
  53. Hong J, Wang L, Zhang T, Zhang B, Chen L. Sigma-1 receptor knockout increases ?-synuclein aggregation and phosphorylation with loss of dopaminergic neurons in substantia nigra. Neurobiol Aging. 2017;59:171-183 pubmed publisher
    ..Levels of phosphorylated eIF2a and C/EBP homologous protein expression were elevated in ?1R-/- mice with decline of ..
  54. Pfeifer I, Elsby R, Fernandez M, Faria P, Nussenzveig D, Lossos I, et al. NFAR-1 and -2 modulate translation and are required for efficient host defense. Proc Natl Acad Sci U S A. 2008;105:4173-8 pubmed publisher
  55. Mazroui R, Sukarieh R, Bordeleau M, Kaufman R, Northcote P, Tanaka J, et al. Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation. Mol Biol Cell. 2006;17:4212-9 pubmed
    ..We propose that SG modeling can occur via both eIF2alpha phosphorylation-dependent and -independent pathways that target translation initiation. ..
  56. Hahn C, Lowrey C. Eukaryotic initiation factor 2? phosphorylation mediates fetal hemoglobin induction through a post-transcriptional mechanism. Blood. 2013;122:477-85 pubmed publisher
    ..Taken together, these findings identify eIF2? phosphorylation as a post-transcriptional regulator of HbF induction that may be pharmacologically targeted, either alone or in combination, in ?-hemoglobinopathy patients. ..
  57. Kusio Kobiałka M. [Pro-survival signaling pathways activated by BCR-ABL oncogene in chronic myelogenous leukemia cells: the role of the perk-EIF2? signal path and acetylation of p53]. Postepy Biochem. 2014;60:401-6 pubmed
  58. Kepp O, Semeraro M, Bravo San Pedro J, Bloy N, Buqué A, Huang X, et al. eIF2α phosphorylation as a biomarker of immunogenic cell death. Semin Cancer Biol. 2015;33:86-92 pubmed publisher
    ..Here, we discuss the role of the ER stress response in ICD and the potential value of eIF2α phosphorylation as a biomarker for this clinically relevant variant of apoptosis. ..
  59. Choy M, Yusoff P, Lee I, Newton J, Goh C, Page R, et al. Structural and Functional Analysis of the GADD34:PP1 eIF2α Phosphatase. Cell Rep. 2015;11:1885-91 pubmed publisher
    ..This work greatly enhances our molecular understanding of a major cellular eIF2α phosphatase and establishes the foundation for future translational work. ..
  60. Placzek A, Molfese D, Khatiwada S, Viana Di Prisco G, Huang W, Sidrauski C, et al. Translational control of nicotine-evoked synaptic potentiation in mice and neuronal responses in human smokers by eIF2α. elife. 2016;5: pubmed publisher
    ..These findings suggest that p-eIF2α regulates synaptic actions of nicotine in both mice and humans, and that reduced p-eIF2α may enhance susceptibility to nicotine (and other drugs of abuse) during adolescence. ..
  61. Merrick W. Mechanism and regulation of eukaryotic protein synthesis. Microbiol Rev. 1992;56:291-315 pubmed
    ..Alternate explanations and various lines of experimentation are proposed to resolve these apparent contradictions. ..
  62. Choi H, Jackson N, Shaw D, Emanuel P, Liu Y, Tousson A, et al. mrtl-A translation/localization regulatory protein encoded within the human c-myc locus and distributed throughout the endoplasmic and nucleoplasmic reticular network. J Cell Biochem. 2008;105:1092-108 pubmed publisher
  63. Lee Y, Cevallos R, Jan E. An upstream open reading frame regulates translation of GADD34 during cellular stresses that induce eIF2alpha phosphorylation. J Biol Chem. 2009;284:6661-73 pubmed publisher
    ..This mechanism may serve as a model for understanding how other 5'UTR uORF-containing mRNAs are regulated during cellular stress. ..
  64. Groskreutz D, Babor E, Monick M, Varga S, Hunninghake G. Respiratory syncytial virus limits alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) phosphorylation to maintain translation and viral replication. J Biol Chem. 2010;285:24023-31 pubmed publisher
    ..The result is limited phosphorylation of eIF2alpha and continued translation of cellular and viral proteins. ..
  65. Carraro V, Maurin A, Lambert Langlais S, Averous J, Chaveroux C, Parry L, et al. Amino acid availability controls TRB3 transcription in liver through the GCN2/eIF2?/ATF4 pathway. PLoS ONE. 2010;5:e15716 pubmed publisher
    ..Therefore, this work establishes for the first time that the molecular mechanisms involved in the regulation of gene transcription by amino acid availability are functional in mouse liver. ..
  66. Saidu N, Touma R, Asali I, Jacob C, Montenarh M. Diallyl tetrasulfane activates both the eIF2? and Nrf2/HO-1 pathways. Biochim Biophys Acta. 2013;1830:2214-25 pubmed publisher
    ..This study shows for the first time a parallel but not equal activation of signaling pathways by DATTS with a competitive ultimate cellular outcome. ..
  67. Gomez E, Powell M, Greenman I, Herbert T. Glucose-stimulated protein synthesis in pancreatic beta-cells parallels an increase in the availability of the translational ternary complex (eIF2-GTP.Met-tRNAi) and the dephosphorylation of eIF2 alpha. J Biol Chem. 2004;279:53937-46 pubmed
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    ..We propose that eIF2alpha phosphorylation is fundamentally a death signal, yet it may promote either death or survival, depending upon coincident signaling events. ..
  69. Rittiner J, Caffall Z, Hernández Martinez R, Sanderson S, Pearson J, Tsukayama K, et al. Functional Genomic Analyses of Mendelian and Sporadic Disease Identify Impaired eIF2α Signaling as a Generalizable Mechanism for Dystonia. Neuron. 2016;92:1238-1251 pubmed publisher
  70. Hasegawa H, Hsu A, Tinberg C, Siegler K, Nazarian A, Tsai M. Single amino acid substitution in LC-CDR1 induces Russell body phenotype that attenuates cellular protein synthesis through eIF2? phosphorylation and thereby downregulates IgG secretion despite operational secretory pathway traffic. MAbs. 2017;9:854-873 pubmed publisher
    ..Consequently, depending on how soon and how severely an antibody-expressing cell develops the RB phenotype, the productive window of Ig secretion can vary widely among the cells expressing different mAbs. ..
  71. Chesnokova E, Bal N, Kolosov P. Kinases of eIF2a Switch Translation of mRNA Subset during Neuronal Plasticity. Int J Mol Sci. 2017;18: pubmed publisher
    ..Of such proteins, we pay close attention to protein kinase M?, which is involved in memory storage and regulated at the translational level. ..
  72. Weiser D, Sikes S, Li S, Shenolikar S. The inhibitor-1 C terminus facilitates hormonal regulation of cellular protein phosphatase-1: functional implications for inhibitor-1 isoforms. J Biol Chem. 2004;279:48904-14 pubmed
    ..This study demonstrates that multiple domains in I-1 target cellular PP1 complexes and establishes I-1 as a cellular regulator of eIF2alpha phosphorylation. ..
  73. Wang J, Laschinger C, Zhao X, Mak B, Seth A, McCulloch C. Mechanical force activates eIF-2alpha phospho-kinases in fibroblast. Biochem Biophys Res Commun. 2005;330:123-30 pubmed
    ..We conclude that phospho-antibody screening is an efficient method for discovery of novel mechanical force-induced phospho-kinases and force can activate eIF-2alpha phospho-kinases in fibroblasts. ..
  74. Jiang Q, He L, Hou Y, Chen J, Duan Y, Deng D, et al. Alpha-ketoglutarate enhances milk protein synthesis by porcine mammary epithelial cells. Amino Acids. 2016;48:2179-88 pubmed publisher
    ..milk-specific proteins (α-lactalbumin and β-casein), mTOR signaling proteins (mTOR, p-mTOR, PERK, p-PERK, eIF2a, P70S6K and p-P70S6K), and endoplasmic reticulum stress (ERS)-associated proteins (BiP and CHOP) in PMEC were ..
  75. Komar A, Gross S, Barth Baus D, Strachan R, Hensold J, Goss Kinzy T, et al. Novel characteristics of the biological properties of the yeast Saccharomyces cerevisiae eukaryotic initiation factor 2A. J Biol Chem. 2005;280:15601-11 pubmed
    Eukaryotic initiation factor 2A (eIF2A) has been shown to direct binding of the initiator methionyl-tRNA (Met-tRNA(i)) to 40 S ribosomal subunits in a codon-dependent manner, in contrast to eIF2, which requires GTP but not the AUG codon ..
  76. Gao J, Zhang Y, Yu C, Tan F, Wang L. Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice. Biochem Biophys Res Commun. 2016;476:326-332 pubmed publisher
    ..for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage...
  77. Huang Y, Ma L, Chen X, Li Z, Huang Y, Shen C, et al. [Genetic polymorphisms of MxA protein and eIF-2a-reg2 and their responses to interferon treatment in patients with chronic hepatitis B]. Zhonghua Gan Zang Bing Za Zhi. 2007;15:187-91 pubmed
    ..05). Patients with GT genotype at MxA promoter -88 responded well to IFN treatment. SNP as a potential marker could be used to predict IFN treatment responses of patients with chronic hepatitis B. ..
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    ..Moreover, 5MP1 is not a GEF but a weak GDI for yeast eIF2. We propose that 5MP1 is a partial mimic and competitor of eIF5, interfering with the key steps by which eIF5 regulates eIF2 function. ..
  79. Liu A, Zhang D, Zhu Y, Gao H, Jiang J, Hu X, et al. Impact of Axis of GHRH and GHRH Receptor on Cell Viability and Apoptosis of the Placental Choriocarcinoma Cell Line. Curr Mol Med. 2016;16:299-311 pubmed
    ..The Most Important Aspect of the Paper: Our present study for the first time provided evidences that GHRH and GHRH-R loops involve in JEG-3 cell viability and apoptosis through Akt and eIF2α pathways. ..
  80. Kwon O, An S, Kim E, Yu J, Hong K, Lee J, et al. An mRNA-specific tRNAi carrier eIF2A plays a pivotal role in cell proliferation under stress conditions: stress-resistant translation of c-Src mRNA is mediated by eIF2A. Nucleic Acids Res. 2017;45:296-310 pubmed publisher
    ..Here, we report that eIF2A, an alternative tRNAi carrier, is responsible for the stress-resistant translation of c-Src mRNA...
  81. Gorrini C, Loreni F, Gandin V, Sala L, Sonenberg N, Marchisio P, et al. Fibronectin controls cap-dependent translation through beta1 integrin and eukaryotic initiation factors 4 and 2 coordinated pathways. Proc Natl Acad Sci U S A. 2005;102:9200-5 pubmed
    ..These findings indicate that integrins may recruit the translational machinery in a unique way and that FN-dependent translation cannot be blocked by mammalian target of rapamycin inhibition. ..
  82. Li Y, Zhang C, Chen X, Yu J, Wang Y, Yang Y, et al. ICP34.5 protein of herpes simplex virus facilitates the initiation of protein translation by bridging eukaryotic initiation factor 2alpha (eIF2alpha) and protein phosphatase 1. J Biol Chem. 2011;286:24785-92 pubmed publisher
    ..We propose that herpes simplex virus protein ICP34.5 bridges PP1 and eIF2? via their binding motifs and thereby facilitates the protein synthesis and viral replication. ..
  83. Rouschop K, Dubois L, Keulers T, van den Beucken T, Lambin P, Bussink J, et al. PERK/eIF2? signaling protects therapy resistant hypoxic cells through induction of glutathione synthesis and protection against ROS. Proc Natl Acad Sci U S A. 2013;110:4622-7 pubmed publisher
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    ..The data demonstrate interplay between key components of dsRNA metabolism, both connecting RHA to an important component of innate immunity and delineating an unanticipated role for PKR in RNA metabolism. ..
  85. Zhang S, Sun Y, Chen H, Dai Y, Zhan Y, Yu S, et al. Activation of the PKR/eIF2? signaling cascade inhibits replication of Newcastle disease virus. Virol J. 2014;11:62 pubmed publisher
    ..PKR is activated by dsRNA generated by NDV infection and inhibits NDV replication by eIF2? phosphorylation. This study provides insight into NDV-host interactions for the development of candidate antiviral strategies. ..
  86. Spurgeon M, Ornelles D. The adenovirus E1B 55-kilodalton and E4 open reading frame 6 proteins limit phosphorylation of eIF2alpha during the late phase of infection. J Virol. 2009;83:9970-82 pubmed publisher
  87. Dong D, Reece E, Yang P. The Nrf2 Activator Vinylsulfone Reduces High Glucose-Induced Neural Tube Defects by Suppressing Cellular Stress and Apoptosis. Reprod Sci. 2016;23:993-1000 pubmed publisher
    ..kinase RNA-like ER kinase (PERK), inositol requiring protein 1α (IRE1a), eukaryotic initiation factor 2α (eIF2a), upregulated C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP), and x-box binding protein 1 (..
  88. Ghosh H, Reizis B, Robbins P. SIRT1 associates with eIF2-alpha and regulates the cellular stress response. Sci Rep. 2011;1:150 pubmed publisher
    ..Finally, SIRT1 co-immunoprecipitates with mediators of eIF2? dephosphorylation, GADD34 and CreP, suggesting a role for SIRT1 in the negative feedback regulation of eIF2? phosphorylation. ..
  89. Liu Q, Peng Y, Zhou P, Qi L, Zhang M, Gao N, et al. 6-Shogaol induces apoptosis in human leukemia cells through a process involving caspase-mediated cleavage of eIF2?. Mol Cancer. 2013;12:135 pubmed publisher
    ..The potent anti-leukemia activity of 6-shogaol found both in vitro and in vivo in our study make this compound a potential anti-tumor agent for hematologic malignancies. ..
  90. Liao Y, Gu F, Mao X, Niu Q, Wang H, Sun Y, et al. Regulation of de novo translation of host cells by manipulation of PERK/PKR and GADD34-PP1 activity during Newcastle disease virus infection. J Gen Virol. 2016;97:867-79 pubmed publisher
    ..Functionally, GADD34, in conjunction with PP1, dephosphorylated eIF2a and restored protein translation, benefiting virus protein synthesis...
  91. Hao C, Duan H, Li H, Pei M, Liu Y, Fan Y, et al. Up-regulation of ANKDR49, a poor prognostic factor, regulates cell proliferation of gliomas. Biosci Rep. 2017;37: pubmed publisher
    ..n-terminal kinase), cleveagated Caspase-7, p-Chk1 (checkpoint kinase 1), and p-eIF2a (eukaryotic translation initiation factor 2a)...
  92. Thiaville M, Pan Y, Gjymishka A, Zhong C, Kaufman R, Kilberg M. MEK signaling is required for phosphorylation of eIF2alpha following amino acid limitation of HepG2 human hepatoma cells. J Biol Chem. 2008;283:10848-57 pubmed publisher
    ..Collectively, these results document a critical interdependence between the MEK-ERK MAPK signaling pathway and the amino acid stress-activated pathway. ..