Gene Symbol: Eif2a
Description: eukaryotic translation initiation factor 2A
Alias: D030048D22, D3Ertd194e, eukaryotic translation initiation factor 2A, eIF-2A
Species: mouse
Products:     Eif2a

Top Publications

  1. Han J, Back S, Hur J, Lin Y, Gildersleeve R, Shan J, et al. ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nat Cell Biol. 2013;15:481-90 pubmed publisher
    ..The findings suggest that limiting protein synthesis will be therapeutic for diseases caused by protein misfolding in the ER. ..
  2. Bevilacqua E, Wang X, Majumder M, Gaccioli F, Yuan C, Wang C, et al. eIF2alpha phosphorylation tips the balance to apoptosis during osmotic stress. J Biol Chem. 2010;285:17098-111 pubmed publisher
    ..We propose that eIF2alpha phosphorylation during hypertonic stress promotes apoptosis by sequestration of specific mRNAs in SGs in a process mediated by the cytoplasmic accumulation of hnRNP A1. ..
  3. Saito A, Hino S, Murakami T, Kanemoto S, Kondo S, Saitoh M, et al. Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis. Nat Cell Biol. 2009;11:1197-204 pubmed publisher
    ..Our findings provide a new link by which ER stress is converted to signalling for the activation of ER-to-Golgi trafficking. ..
  4. Oyadomari S, Harding H, Zhang Y, Oyadomari M, Ron D. Dephosphorylation of translation initiation factor 2alpha enhances glucose tolerance and attenuates hepatosteatosis in mice. Cell Metab. 2008;7:520-32 pubmed publisher
    ..These observations suggest that eIF2(alphaP)-mediated translation of key hepatic transcriptional regulators of intermediary metabolism contributes to the detrimental consequences of nutrient excess. ..
  5. Gomez E, Powell M, Bevington A, Herbert T. A decrease in cellular energy status stimulates PERK-dependent eIF2alpha phosphorylation and regulates protein synthesis in pancreatic beta-cells. Biochem J. 2008;410:485-93 pubmed
    ..In summary, we show that PERK is activated at low glucose concentrations in response to a decrease in energy status and that this plays an important role in glucose-regulated protein synthesis in pancreatic beta-cells. ..
  6. Zhou D, Palam L, Jiang L, Narasimhan J, Staschke K, Wek R. Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditions. J Biol Chem. 2008;283:7064-73 pubmed publisher
    ..These results demonstrate that eIF2 kinases direct the translational expression of multiple transcription regulators by a mechanism involving delayed translation reinitiation. ..
  7. 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. ..
  8. 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. ..
  9. Harding H, Zhang Y, Scheuner D, Chen J, Kaufman R, Ron D. Ppp1r15 gene knockout reveals an essential role for translation initiation factor 2 alpha (eIF2alpha) dephosphorylation in mammalian development. Proc Natl Acad Sci U S A. 2009;106:1832-7 pubmed publisher
    ..These loss-of-function phenotypes are rescued by a mutation, Eif2a(S51A), that prevents regulated phosphorylation of eIF2alpha...

More Information


  1. Han J, Murthy R, Wood B, Song B, Wang S, Sun B, et al. ER stress signalling through eIF2? and CHOP, but not IRE1?, attenuates adipogenesis in mice. Diabetologia. 2013;56:911-24 pubmed publisher
    ..These results demonstrate that eIF2?-CHOP suppresses adipogenesis and limits expansion of fat mass in vivo in mice, rendering this pathway a potential therapeutic target. ..
  2. Zhang X, Szabo E, Michalak M, Opas M. Endoplasmic reticulum stress during the embryonic development of the central nervous system in the mouse. Int J Dev Neurosci. 2007;25:455-63 pubmed
    ..Furthermore, our data suggest that ER stress-like mechanism may induce apoptosis via activation of the caspases during embryonic development of the central nervous system. ..
  3. Furuya S, Yoshida K, Kawakami Y, Yang J, Sayano T, Azuma N, et al. Inactivation of the 3-phosphoglycerate dehydrogenase gene in mice: changes in gene expression and associated regulatory networks resulting from serine deficiency. Funct Integr Genomics. 2008;8:235-49 pubmed publisher
    ..These observations suggest that Phgdh inactivation alters transcriptional programs in several regulatory networks. ..
  4. Sadighi Akha A, Theriot C, Erb Downward J, McDermott A, Falkowski N, Tyra H, et al. Acute infection of mice with Clostridium difficile leads to eIF2? phosphorylation and pro-survival signalling as part of the mucosal inflammatory response. Immunology. 2013;140:111-22 pubmed publisher
    ..difficile and highlight eIF2? phosphorylation and the interleukin-22-pSTAT3-RegIII? axis as two of the pathways that could be used to contain and counteract the damage inflicted on the intestinal epithelium. ..
  5. Ito T, Jagus R, May W. Interleukin 3 stimulates protein synthesis by regulating double-stranded RNA-dependent protein kinase. Proc Natl Acad Sci U S A. 1994;91:7455-9 pubmed
    ..Thus, IL-3 appears to positively regulate protein synthesis by inducing the inactivation of PKR in a growth factor signaling pathway. ..
  6. Wang L, Zhang S, Wang Z, Xu M, Yuan L, Cui J, et al. A protective role of Heme-regulated eIF2? kinase in cadmium-induced liver and kidney injuries. Chemosphere. 2017;185:284-289 pubmed publisher
    ..Our results further extended the understanding of HRI on the regulation of non-erythroid lineages and might provide new aspects for preventing and treating Cd-induced detrimental effects. ..
  7. Alter J, Bengal E. Stress-induced C/EBP homology protein (CHOP) represses MyoD transcription to delay myoblast differentiation. PLoS ONE. 2011;6:e29498 pubmed publisher
    ..This protein complex may reduce histone acetylation when bound to MyoD regulatory regions. Overall, our results suggest that the activation of a stress pathway in myoblasts transiently downregulate the myogenic program. ..
  8. Iwawaki T, Akai R, Yamanaka S, Kohno K. Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability. Proc Natl Acad Sci U S A. 2009;106:16657-62 pubmed publisher
    ..These findings reveal that IRE1alpha plays an essential function in extraembryonic tissues and highlight the relationship of physiological ER stress and angiogenesis in the placenta during pregnancy in mammals. ..
  9. Reineke L, Dougherty J, Pierre P, Lloyd R. Large G3BP-induced granules trigger eIF2? phosphorylation. Mol Biol Cell. 2012;23:3499-510 pubmed publisher
    ..Furthermore, these data suggest that stress granules are active in signaling to the translational machinery and may be important regulators of the innate immune response...
  10. Kim M, Aydemir T, Cousins R. Dietary Zinc Regulates Apoptosis through the Phosphorylated Eukaryotic Initiation Factor 2?/Activating Transcription Factor-4/C/EBP-Homologous Protein Pathway during Pharmacologically Induced Endoplasmic Reticulum Stress in Livers of Mice. J Nutr. 2016;146:2180-2186 pubmed
  11. 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
  12. Saito A, Ochiai K, Kondo S, Tsumagari K, Murakami T, Cavener D, et al. Endoplasmic reticulum stress response mediated by the PERK-eIF2(alpha)-ATF4 pathway is involved in osteoblast differentiation induced by BMP2. J Biol Chem. 2011;286:4809-18 pubmed publisher
    ..Taken together, ER stress occurs during osteoblast differentiation and activates the PERK-eIF2?-ATF4 signaling pathway followed by the promotion of gene expression essential for osteogenesis, such as Ocn and Bsp. ..
  13. Pena J, Harris E. Dengue virus modulates the unfolded protein response in a time-dependent manner. J Biol Chem. 2011;286:14226-36 pubmed publisher
    ..These results demonstrate that time-dependent activation of the unfolded protein response by DENV-2 can override inhibition of translation, prevent apoptosis, and prolong the viral life cycle. ..
  14. Huang W, Placzek A, Viana Di Prisco G, Khatiwada S, Sidrauski C, Krnjević K, et al. Translational control by eIF2α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine. elife. 2016;5: pubmed publisher
    ..Thus, during addiction, cocaine hijacks translational control by p-eIF2α, initiating synaptic potentiation and addiction-related behaviors. These insights may hold promise for new treatments for addiction. ..
  15. Birkenfeld A, Lee H, Majumdar S, Jurczak M, Camporez J, Jornayvaz F, et al. Influence of the hepatic eukaryotic initiation factor 2alpha (eIF2alpha) endoplasmic reticulum (ER) stress response pathway on insulin-mediated ER stress and hepatic and peripheral glucose metabolism. J Biol Chem. 2011;286:36163-70 pubmed publisher
    ..Finally, eIF2α is crucial for proper resolution of insulin-induced ER stress. ..
  16. Bobrovnikova Marjon E, Hatzivassiliou G, Grigoriadou C, Romero M, Cavener D, Thompson C, et al. PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation. Proc Natl Acad Sci U S A. 2008;105:16314-9 pubmed publisher
    ..These findings implicate PERK as a physiologically relevant regulator of the lipogenic pathway...
  17. Papadakis A, Paraskeva E, Peidis P, Muaddi H, Li S, Raptis L, et al. eIF2{alpha} Kinase PKR modulates the hypoxic response by Stat3-dependent transcriptional suppression of HIF-1{alpha}. Cancer Res. 2010;70:7820-9 pubmed publisher
    ..Our findings reveal a novel tumor suppressor function for PKR, which inhibits HIF-1? expression through Stat3 but is independent of eIF2? phosphorylation. ..
  18. Zhu M, Tao J, Vasievich M, Wei W, Zhu G, Khoriaty R, et al. Neural tube opening and abnormal extraembryonic membrane development in SEC23A deficient mice. Sci Rep. 2015;5:15471 pubmed publisher
    ..Our results suggest that mammalian SEC23A and SEC23B transport overlapping yet distinct spectra of cargo in vivo. ..
  19. Chaveroux C, Carraro V, Canaple L, Averous J, Maurin A, Jousse C, et al. In vivo imaging of the spatiotemporal activity of the eIF2α-ATF4 signaling pathway: Insights into stress and related disorders. Sci Signal. 2015;8:rs5 pubmed publisher
    ..The CARE-LUC mouse model represents an innovative tool to investigate the eIF2α-ATF4 axis and to develop drugs targeting this important pathway in the remediation of related pathologies. ..
  20. Firtina Z, Danysh B, Bai X, Gould D, Kobayashi T, Duncan M. Abnormal expression of collagen IV in lens activates unfolded protein response resulting in cataract. J Biol Chem. 2009;284:35872-84 pubmed publisher
    ..Collectively, the results provide in vivo evidence for a role of UPR in cataract formation in response to accumulation of terminally unfolded proteins in the endoplasmic reticulum. ..
  21. Suraweera A, Münch C, Hanssum A, Bertolotti A. Failure of amino acid homeostasis causes cell death following proteasome inhibition. Mol Cell. 2012;48:242-53 pubmed publisher
    ..These results reveal that cells can tolerate protein waste, but not the amino acid scarcity resulting from proteasome inhibition. ..
  22. Sakhatskyy P, Gabino Miranda G, Newton J, Lee C, Choudhary G, Vang A, et al. Cigarette smoke-induced lung endothelial apoptosis and emphysema are associated with impairment of FAK and eIF2?. Microvasc Res. 2014;94:80-9 pubmed publisher
    ..Taken together, our data suggest that inhibition of eIF2? and FAK signaling may play an important role in CS-induced lung EC apoptosis and emphysema. ..
  23. Kaneko K, Xu P, Cordonier E, Chen S, Ng A, Xu Y, et al. Neuronal Rap1 Regulates Energy Balance, Glucose Homeostasis, and Leptin Actions. Cell Rep. 2016;16:3003-3015 pubmed publisher
    ..Thus, neuronal Rap1 critically regulates leptin sensitivity and mediates HFD-induced obesity and hypothalamic pathology and may represent a potential therapeutic target for obesity treatment. ..
  24. Hori O, Miyazaki M, Tamatani T, Ozawa K, Takano K, Okabe M, et al. Deletion of SERP1/RAMP4, a component of the endoplasmic reticulum (ER) translocation sites, leads to ER stress. Mol Cell Biol. 2006;26:4257-67 pubmed
  25. 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. ..
  26. Datta B, Majumdar A, Datta R, Balusu R. Treatment of cells with the angiogenic inhibitor fumagillin results in increased stability of eukaryotic initiation factor 2-associated glycoprotein, p67, and reduced phosphorylation of extracellular signal-regulated kinases. Biochemistry. 2004;43:14821-31 pubmed
    ..These results suggest that fumagillin increases the stability of p67 and its affinity to ERKs 1 and 2 and causes the inhibition of the phosphorylation of ERKs 1 and 2. ..
  27. Zismanov V, Chichkov V, Colangelo V, Jamet S, Wang S, Syme A, et al. Phosphorylation of eIF2α Is a Translational Control Mechanism Regulating Muscle Stem Cell Quiescence and Self-Renewal. Cell Stem Cell. 2016;18:79-90 pubmed publisher
    ..Pharmacological inhibition of eIF2α dephosphorylation enhances skeletal muscle stem cell self-renewal and regenerative capacity. ..
  28. 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. ..
  29. 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. ..
  30. Huang M, Sivagurunathan S, Ting S, Jansson P, Austin C, Kelly M, et al. Molecular and functional alterations in a mouse cardiac model of Friedreich ataxia: activation of the integrated stress response, eIF2? phosphorylation, and the induction of downstream targets. Am J Pathol. 2013;183:745-57 pubmed publisher
    ..Thus, the pathogenesis of cardiomyopathy in FA correlates with the early and persistent eIF2? phosphorylation, which precedes activation of autophagy and apoptosis. ..
  31. Fujimura K, Sasaki A, Anderson P. Selenite targets eIF4E-binding protein-1 to inhibit translation initiation and induce the assembly of non-canonical stress granules. Nucleic Acids Res. 2012;40:8099-110 pubmed publisher
    ..Our results reveal a new mechanism of mammalian SG assembly and provide insights into how selenite cytotoxicity may be exploited as an anti-neoplastic therapy. ..
  32. Wylie K, Schrimpf J, Morrison L. Increased eIF2alpha phosphorylation attenuates replication of herpes simplex virus 2 vhs mutants in mouse embryonic fibroblasts and correlates with reduced accumulation of the PKR antagonist ICP34.5. J Virol. 2009;83:9151-62 pubmed publisher
    ..5 does not accumulate efficiently in MEFs infected with HSV-2 vhs mutant viruses, suggesting that the accumulation of phosphorylated eIF2alpha and the attenuated phenotype of HSV-2 vhs mutants in MEFs result from a deficiency in ICP34.5. ..
  33. Huang H, Miao L, Liang F, Liu X, Xu L, Teng X, et al. Neuroprotection by eIF2?-CHOP inhibition and XBP-1 activation in EAE/optic neuritiss. Cell Death Dis. 2017;8:e2936 pubmed publisher
    ..This finding adds to the evidence that ER stress is a general upstream mechanism for neurodegeneration and suggests that targeting ER stress molecules is a promising therapeutic strategy for neuroprotection in MS. ..
  34. 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 ..
  35. Sayano T, Kawakami Y, Kusada W, Suzuki T, Kawano Y, Watanabe A, et al. L-serine deficiency caused by genetic Phgdh deletion leads to robust induction of 4E-BP1 and subsequent repression of translation initiation in the developing central nervous system. FEBS J. 2013;280:1502-17 pubmed publisher
    ..These data suggest that elevated levels of 4E-BP1 may be involved in a mechanism to arrest brain development in Phgdh KO embryos. ..
  36. Li X, Xu C, Yang P. c-Jun NH2-terminal kinase 1/2 and endoplasmic reticulum stress as interdependent and reciprocal causation in diabetic embryopathy. Diabetes. 2013;62:599-608 pubmed publisher
    ..Suppressing JNK1/2 activation by either jnk1 or jnk2 gene deletion prevents ER stress. Thus, our study reveals a reciprocal causation of ER stress and JNK1/2 in mediating the teratogenicity of maternal diabetes. ..
  37. Liu L, Wise D, Diehl J, Simon M. Hypoxic reactive oxygen species regulate the integrated stress response and cell survival. J Biol Chem. 2008;283:31153-62 pubmed publisher
    ..Collectively, our data support an important role for ROS in hypoxic cell survival. Under conditions of moderate hypoxia, ROS induce the ISR, thereby promoting energy and redox homeostasis and enhancing cellular survival. ..
  38. Firtina Z, Duncan M. Unfolded Protein Response (UPR) is activated during normal lens development. Gene Expr Patterns. 2011;11:135-43 pubmed publisher
    ..These results propose a role for UPR activation in lens fiber cell differentiation during embryogenesis. ..
  39. Saito A, Kanemoto S, Zhang Y, Asada R, Hino K, Imaizumi K. Chondrocyte proliferation regulated by secreted luminal domain of ER stress transducer BBF2H7/CREB3L2. Mol Cell. 2014;53:127-39 pubmed publisher
    ..The dual N- and C-terminal functions of BBF2H7 triggered by physiological ER stress may allow chondrocytes to simultaneously regulate distinct cellular events for differentiation and proliferation in developing cartilage. ..
  40. Yoon J, Park K, Hwang D, Rhee K. Importance of eIF2α phosphorylation as a protective mechanism against heat stress in mouse male germ cells. Mol Reprod Dev. 2017;84:265-274 pubmed publisher
    ..Mol. Reprod. Dev. 84: 265-274, 2017. © 2017 Wiley Periodicals, Inc. ..
  41. Shrestha N, Bahnan W, Wiley D, Barber G, Fields K, Schesser K. Eukaryotic initiation factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion. J Biol Chem. 2012;287:28738-44 pubmed publisher
    ..Collectively, our data indicate that the highly conserved eIF2 signaling pathway, which is vitally important for antiviral responses, plays a variety of heretofore unrecognized roles in antibacterial responses. ..
  42. Emara M, Fujimura K, Sciaranghella D, Ivanova V, Ivanov P, Anderson P. Hydrogen peroxide induces stress granule formation independent of eIF2? phosphorylation. Biochem Biophys Res Commun. 2012;423:763-9 pubmed publisher
    ..Our data reveal new aspects of translational regulation induced by oxidative insults...
  43. Zhao Z, Cao L, Reece E. Formation of neurodegenerative aggresome and death-inducing signaling complex in maternal diabetes-induced neural tube defects. Proc Natl Acad Sci U S A. 2017;114:4489-4494 pubmed publisher
    ..Enhancing protein folding could be a potential interventional approach to preventing embryonic malformations in diabetic pregnancies. ..
  44. Kraushar M, Thompson K, Wijeratne H, Viljetić B, Sakers K, Marson J, et al. Temporally defined neocortical translation and polysome assembly are determined by the RNA-binding protein Hu antigen R. Proc Natl Acad Sci U S A. 2014;111:E3815-24 pubmed publisher
    ..Our study identifies a crucial role for HuR in neocortical development as a translational gatekeeper for functionally related mRNA subgroups and polysomal protein specificity. ..
  45. 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. ..
  46. Stone S, Ho Y, Li X, Jamison S, Harding H, Ron D, et al. Dual role of the integrated stress response in medulloblastoma tumorigenesis. Oncotarget. 2016;7:64124-64135 pubmed publisher
    ..Collectively, these data imply the dual role of the ISR, promoting and inhibiting, in medulloblastoma tumorigenesis by regulating apoptosis of pre-malignant GCPs during the course of malignant transformation. ..
  47. 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. ..
  48. Alves V, Motta F, Roffe M, Delamano A, Pesquero J, Castilho B. GCN2 activation and eIF2alpha phosphorylation in the maturation of mouse oocytes. Biochem Biophys Res Commun. 2009;378:41-4 pubmed publisher
    ..After fertilization, eIF2alpha phosphorylation decreases drastically. These results suggest that GCN2 mediated translational control may contribute to regulatory mechanisms operating during oocyte maturation. ..
  49. Wang X, Rao R, Kosakowska Cholody T, Masood M, Southon E, Zhang H, et al. Mitochondrial degeneration and not apoptosis is the primary cause of embryonic lethality in ceramide transfer protein mutant mice. J Cell Biol. 2009;184:143-58 pubmed publisher
    ..Thus, global compromise of ER and mitochondrial integrity caused by ceramide accumulation in CERT mutant mice primarily affects organogenesis rather than causing cell death via apoptotic pathways. ..
  50. Miyake M, Nomura A, Ogura A, Takehana K, Kitahara Y, Takahara K, et al. Skeletal muscle-specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21-mediated non-cell-autonomous energy metabolism. FASEB J. 2016;30:798-812 pubmed publisher
    ..Our findings establish that eIF2α phosphorylation regulates not only cell-autonomous proteostasis and amino acid metabolism, but also affects non-cell-autonomous metabolic regulation by induced expression of a potent myokine. ..
  51. Lin W, Lin Y, Li J, Harding H, Ron D, Jamison S. A deregulated integrated stress response promotes interferon-γ-induced medulloblastoma. J Neurosci Res. 2011;89:1586-95 pubmed publisher
    ..Thus, our data provide genetic evidence that the ISR facilitates medulloblastoma development. ..
  52. Domingo Gil E, Perez Jimenez E, Ventoso I, Najera J, Esteban M. Expression of the E3L gene of vaccinia virus in transgenic mice decreases host resistance to vaccinia virus and Leishmania major infections. J Virol. 2008;82:254-67 pubmed
    ..These results demonstrate that expression of the E3L gene in transgenic mice partly reverses the resistance of the host to viral and parasitic infections and that these effects are associated with immune alterations...
  53. 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. ..
  54. 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
  55. Panzhinskiy E, Ren J, Nair S. Protein tyrosine phosphatase 1B and insulin resistance: role of endoplasmic reticulum stress/reactive oxygen species/nuclear factor kappa B axis. PLoS ONE. 2013;8:e77228 pubmed publisher
    ..Our data suggest that PTP1B is induced by ER stress via the activation of the ROS-NF?B axis which is causes unfolded protein response and mediates insulin resistance in the skeletal muscle under obese condition. ..
  56. Cao S, Wang M, Harrington J, Chuang B, Eckmann L, Kaufman R. Phosphorylation of eIF2? is dispensable for differentiation but required at a posttranscriptional level for paneth cell function and intestinal homeostasis in mice. Inflamm Bowel Dis. 2014;20:712-22 pubmed publisher
    ..We conclude eIF2? phosphorylation is required for the normal function of intestinal Paneth cells and mucosal homeostasis by activating UPR signaling and promoting messenger RNA recruitment to the ER membrane for translation. ..
  57. Maurin A, Benani A, Lorsignol A, Brenachot X, Parry L, Carraro V, et al. Hypothalamic eIF2α signaling regulates food intake. Cell Rep. 2014;6:438-44 pubmed publisher
  58. Li H, Zhou B, Liu J, Li F, Li Y, Kang X, et al. Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner. Cell Cycle. 2015;14:1893-907 pubmed publisher
    ..Collectively, our findings supported the notion that PGRN is a key regulator of insulin resistance and that PGRN may mediate its effects, at least in part, by inducing ER stress via the PERK-eIF2α dependent pathway. ..
  59. Kimball S, Jefferson L. Induction of REDD1 gene expression in the liver in response to endoplasmic reticulum stress is mediated through a PERK, eIF2? phosphorylation, ATF4-dependent cascade. Biochem Biophys Res Commun. 2012;427:485-9 pubmed publisher
    ..Moreover, the induction of REDD1 gene expression was shown to require the protein kinase PERK and enhanced phosphorylation of its substrate, the ?-subunit of eukaryotic initiation factor 2. ..
  60. Muaddi H, Majumder M, Peidis P, Papadakis A, Holcik M, Scheuner D, et al. Phosphorylation of eIF2? at serine 51 is an important determinant of cell survival and adaptation to glucose deficiency. Mol Biol Cell. 2010;21:3220-31 pubmed publisher
    ..Our data demonstrate that eIF2? phosphorylation is a significant determinant of survival and adaptation of glucose-deficient cells with possible important implications in biological processes that interfere with glucose metabolism. ..
  61. Tărlungeanu D, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, et al. Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder. Cell. 2016;167:1481-1494.e18 pubmed publisher
    ..Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function. ..
  62. Majumder M, Huang C, Snider M, Komar A, Tanaka J, Kaufman R, et al. A novel feedback loop regulates the response to endoplasmic reticulum stress via the cooperation of cytoplasmic splicing and mRNA translation. Mol Cell Biol. 2012;32:992-1003 pubmed publisher
    ..We propose a model in which eIF2? phosphorylation-mediated control of mRNA turnover is a molecular switch that regulates the stress response transcription program and the ER's capacity for protein folding during stress. ..
  63. Yadav V, Gao X, Willard B, Hatzoglou M, Banerjee R, Kabil O. Hydrogen sulfide modulates eukaryotic translation initiation factor 2? (eIF2?) phosphorylation status in the integrated stress-response pathway. J Biol Chem. 2017;292:13143-13153 pubmed publisher
    ..Although a transient increase in endogenous H2S production provides cytoprotection, its chronic increase such as in cystathionine ?-synthase deficiency may pose a problem. ..