EIF2A

Summary

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. Fribley A, Evenchik B, Zeng Q, Park B, Guan J, Zhang H, et al. Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa. J Biol Chem. 2006;281:31440-7 pubmed
  2. 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. ..
  3. 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. ..
  4. 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.
  5. 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. 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...
  6. 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), ..
  7. 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...
  8. 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
  9. 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...
  10. 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...

Detail Information

Publications90

  1. Fribley A, Evenchik B, Zeng Q, Park B, Guan J, Zhang H, et al. Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa. J Biol Chem. 2006;281:31440-7 pubmed
  2. 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. ..
  3. 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. ..
  4. 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.
  5. 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. 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...
  6. 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), ..
  7. 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...
  8. 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
  9. 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...
  10. 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...
  11. 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...
  12. 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 ..
  13. Bretin A, Carrière J, Dalmasso G, Bergougnoux A, B chir W, Maurin A, et al. Activation of the EIF2AK4-EIF2A/eIF2α-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/eIF2α-ATF4 pathway in the autophagic response to AIEC infection...
  14. 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 ..
  15. 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)...
  16. 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...
  17. 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 (..
  18. 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...
  19. 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...
  20. 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)...
  21. 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...
  22. 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...
  23. 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, ..
  24. 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 ..
  25. 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...
  26. 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...
  27. 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. ..
  28. 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 ..
  29. 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...
  30. 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
  31. 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. ..
  32. 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
  33. 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. ..
  34. 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. ..
  35. 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. ..
  36. 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. ..
  37. 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. ..
  38. 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
  39. 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. ..
  40. 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. ..
  41. 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. ..
  42. 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. ..
  43. Scheuner D, Patel R, Wang F, Lee K, Kumar K, Wu J, et al. Double-stranded RNA-dependent protein kinase phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 mediates apoptosis. J Biol Chem. 2006;281:21458-68 pubmed
    ..We propose that eIF2alpha phosphorylation is fundamentally a death signal, yet it may promote either death or survival, depending upon coincident signaling events. ..
  44. 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
  45. 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 eIF2α 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. ..
  46. 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 eIF2? Signaling as a Generalizable Mechanism for Dystonia. Neuron. 2016;92:1238-1251 pubmed publisher
  47. 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. ..
  48. 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. ..
  49. 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. ..
  50. 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 ..
  51. 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 ..
  52. 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...
  53. Singh C, Watanabe R, Zhou D, Jennings M, Fukao A, Lee B, et al. Mechanisms of translational regulation by a human eIF5-mimic protein. Nucleic Acids Res. 2011;39:8314-28 pubmed publisher
    ..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. ..
  54. 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. ..
  55. 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...
  56. 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. ..
  57. 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. ..
  58. 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
  59. 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. ..
  60. Sadler A, Latchoumanin O, Hawkes D, Mak J, Williams B. An antiviral response directed by PKR phosphorylation of the RNA helicase A. PLoS Pathog. 2009;5:e1000311 pubmed publisher
    ..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. ..
  61. 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. ..
  62. 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
  63. 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 (..
  64. 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. ..
  65. 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)...
  66. 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. ..
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    ..However, MCF-7 cells did not show such synergic effects. These results suggest that dephosphorylation of eIF2α by GADD34 plays an important role in doxorubicin resistance in MCF-7/ADR cells. ..
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