eIF-2alpha

Summary

Gene Symbol: eIF-2alpha
Description: eukaryotic translation Initiation Factor 2alpha
Alias: CG9946, Dmel\CG9946, EIF-2alpha, Eif2alpha, IF2A_DROME, M(1)14C, M(1)19-153, M(1)8e3-10, deIF2alpha, eIF-2, eIF-2 a, eIF-2 alpha, eIF-2alphaeIF-2alpha, eIF2 alpha, eIF2-alpha, eIF2a, eIF2alpha, eiF-2alpha, elF2alpha, l(1)14Cf, l(1)19-153, eukaryotic translation initiation factor 2alpha, CG9946-PA, CG9946-PB, eIF-2alpha-PA, eIF-2alpha-PB, eukaryotic initiation factor 2alpha, eukaryotic translation initiation factor 2, minute (1) 14C
Species: fruit fly
Products:     eIF-2alpha

Top Publications

  1. Garrey J, Lee Y, Au H, Bushell M, Jan E. Host and viral translational mechanisms during cricket paralysis virus infection. J Virol. 2010;84:1124-38 pubmed publisher
    ..of eukaryotic translation initiation factor 4G (eIF4G) and eIF4E early in infection and the induction of deIF2alpha phosphorylation at 3 h postinfection, which lags after the initial inhibition of host translation...
  2. Farny N, Kedersha N, Silver P. Metazoan stress granule assembly is mediated by P-eIF2alpha-dependent and -independent mechanisms. RNA. 2009;15:1814-21 pubmed publisher
    ..We further examine the role of the two Drosophila eIF2alpha kinases, PEK and GCN2, in regulating SG formation in response to heat and arsenite stress...
  3. Haecker A, Bergman M, Neupert C, Moussian B, Luschnig S, Aebi M, et al. Wollknauel is required for embryo patterning and encodes the Drosophila ALG5 UDP-glucose:dolichyl-phosphate glucosyltransferase. Development. 2008;135:1745-9 pubmed publisher
    ..As a result, phosphorylation of the translation factor eIF2alpha is increased...
  4. Kim H, Raphael A, LADOW E, McGurk L, Weber R, Trojanowski J, et al. Therapeutic modulation of eIF2? phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nat Genet. 2014;46:152-60 pubmed publisher
    ..These findings indicate that the dysfunction induced by prolonged stress granule formation might contribute directly to ALS and that compounds that mitigate this process may represent a novel therapeutic approach. ..
  5. Keplinger B, Rabetoy A, Cavener D. A somatic reproductive organ enhancer complex activates expression in both the developing and the mature Drosophila reproductive tract. Dev Biol. 1996;180:311-23 pubmed
    ..A model of the evolution of Gld expression in the ejaculatory duct and oviduct is presented. ..
  6. Qu S, Perlaky S, Organ E, Crawford D, Cavener D. Mutations at the Ser50 residue of translation factor eIF-2alpha dominantly affect developmental rate, body weight, and viability of Drosophila melanogaster. Gene Expr. 1997;6:349-60 pubmed
    ..The HD transgenic flies exhibit a relatively lower level of global protein synthesis than the HA transgenic flies, although the difference is statistically insignificant. ..
  7. Banga S, Yamamoto A, Mason J, Boyd J. Molecular cloning of mei-41, a gene that influences both somatic and germline chromosome metabolism of Drosophila melanogaster. Mol Gen Genet. 1995;246:148-55 pubmed
    ..This study provides the foundation for molecular analysis of a function that is essential for chromosome stability in both the germline and somatic cells. ..
  8. Gareau C, Houssin E, Martel D, Coudert L, Mellaoui S, Huot M, et al. Characterization of fragile X mental retardation protein recruitment and dynamics in Drosophila stress granules. PLoS ONE. 2013;8:e55342 pubmed publisher
    ..To our knowledge, this is the first demonstration of the regulated shuttling activity of a SG component between RNA granules and the cytosol. ..
  9. Williams D, Pavitt G, Proud C. Characterization of the initiation factor eIF2B and its regulation in Drosophila melanogaster. J Biol Chem. 2001;276:3733-42 pubmed
    ..In mammals and yeast, its activity is regulated by phosphorylation of eIF2alpha. Here we have cloned Drosophila melanogaster cDNAs encoding polypeptides showing substantial similarity to eIF2B ..

More Information

Publications40

  1. Demontis F, Piccirillo R, Goldberg A, Perrimon N. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models. Dis Model Mech. 2013;6:1339-52 pubmed publisher
  2. Lindström R, Lindholm P, Kallijärvi J, Palgi M, Saarma M, Heino T. Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster. PLoS ONE. 2016;11:e0151550 pubmed publisher
    ..Our data suggest a role for Manf in the regulation of Drosophila UPR. ..
  3. McKim K, Dahmus J, Hawley R. Cloning of the Drosophila melanogaster meiotic recombination gene mei-218: a genetic and molecular analysis of interval 15E. Genetics. 1996;144:215-28 pubmed
    ..The mei-218 gene is predicted to produce an 1186-amino acid protein that has no significant similarities to any known proteins. ..
  4. Pomar N, Berlanga J, Campuzano S, Hernández G, Elías M, de Haro C. Functional characterization of Drosophila melanogaster PERK eukaryotic initiation factor 2alpha (eIF2alpha) kinase. Eur J Biochem. 2003;270:293-306 pubmed
    Four distinct eukaryotic initiation factor 2alpha (eIF2alpha) kinases phosphorylate eIF2alpha at S51 and regulate protein synthesis in response to various environmental stresses...
  5. Maor G, Rencus Lazar S, Filocamo M, Steller H, Segal D, Horowitz M. Unfolded protein response in Gaucher disease: from human to Drosophila. Orphanet J Rare Dis. 2013;8:140 pubmed publisher
    ..Our results strongly suggest that mutant GCase induces the UPR in GD patients as well as in carriers of GD mutations and leads to development of locomotion deficit in flies heterozygous for GD mutations. ..
  6. Andersen D, Leevers S. The essential Drosophila ATP-binding cassette domain protein, pixie, binds the 40 S ribosome in an ATP-dependent manner and is required for translation initiation. J Biol Chem. 2007;282:14752-60 pubmed
    ..Thus, the function of this soluble ATP-binding cassette domain protein family in translation initiation has been conserved from yeast through to higher eukaryotes...
  7. Rojas Benítez D, Thiaville P, de Crécy Lagard V, Glavic A. The Levels of a Universally Conserved tRNA Modification Regulate Cell Growth. J Biol Chem. 2015;290:18699-707 pubmed publisher
    ..These findings reveal an unprecedented relationship between the translation machinery and TOR, where translation efficiency, limited by the availability of t(6)A-modified tRNA, determines growth potential in eukaryotic cells. ..
  8. Zapata J, Maroto F, Sierra J. Inactivation of mRNA cap-binding protein complex in Drosophila melanogaster embryos under heat shock. J Biol Chem. 1991;266:16007-14 pubmed
    ..Together, the above results suggest that some modification leading to the disruption of Drosophila CBP complex may account, at least to some extent, for the mRNA discrimination established in heat-shocked Drosophila embryos. ..
  9. Gibert J, Mouchel Vielh E, De Castro S, Peronnet F. Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary Hotspot Gene tan in Drosophila melanogaster. PLoS Genet. 2016;12:e1006218 pubmed publisher
    ..Sensitivity of t expression to environmental conditions might therefore give more substrate for selection, explaining why this gene has frequently been involved in evolution of pigmentation. ..
  10. Gareau C, Martel D, Coudert L, Mellaoui S, Mazroui R. Characterization of Fragile X Mental Retardation Protein granules formation and dynamics in Drosophila. Biol Open. 2013;2:68-81 pubmed publisher
    ..This study opens new avenues to further elucidate the molecular mechanisms controlling FMRP trafficking with its associated mRNAs in and out of RNA granules. ..
  11. Brown N. Null mutations in the alpha PS2 and beta PS integrin subunit genes have distinct phenotypes. Development. 1994;120:1221-31 pubmed
  12. Nagy P, Varga A, Pircs K, Hegedűs K, Juhász G. Myc-driven overgrowth requires unfolded protein response-mediated induction of autophagy and antioxidant responses in Drosophila melanogaster. PLoS Genet. 2013;9:e1003664 pubmed publisher
    ..These novel results give additional support for finding future approaches to specifically inhibit the growth of cancer cells addicted to oncogenic Myc. ..
  13. Carra S, Boncoraglio A, Kanon B, Brunsting J, Minoia M, Rana A, et al. Identification of the Drosophila ortholog of HSPB8: implication of HSPB8 loss of function in protein folding diseases. J Biol Chem. 2010;285:37811-22 pubmed publisher
    ..Our current data further support the link between the HSPB8-BAG3 complex, autophagy, and folding diseases and demonstrate that impairment or loss of function of HSPB8 might accelerate the progression and/or severity of folding diseases. ..
  14. Ryoo H, Steller H. Unfolded protein response in Drosophila: why another model can make it fly. Cell Cycle. 2007;6:830-5 pubmed
    ..Here, we review the molecular components of the Drosophila UPR as well as the disease models that may be affected by this signaling pathway. ..
  15. Duncan R, Cavener D, Qu S. Heat shock effects on phosphorylation of protein synthesis initiation factor proteins eIF-4E and eIF-2 alpha in Drosophila. Biochemistry. 1995;34:2985-97 pubmed
    ..Several distinctive characteristics of this phosphoprotein suggest it is Drosophila eIF-4B. ..
  16. Sánchez Alvarez M, Zhang Q, Finger F, Wakelam M, Bakal C. Cell cycle progression is an essential regulatory component of phospholipid metabolism and membrane homeostasis. Open Biol. 2015;5:150093 pubmed publisher
    ..We propose that coupling lipid metabolism to cell cycle progression is a means by which cells have evolved to coordinate proliferation with cell and organelle growth. ..
  17. Mounir Z, Krishnamoorthy J, Wang S, Papadopoulou B, Campbell S, Muller W, et al. Akt determines cell fate through inhibition of the PERK-eIF2? phosphorylation pathway. Sci Signal. 2011;4:ra62 pubmed publisher
    ..to various forms of environmental stress by inducing the phosphorylation of the ? subunit of eukaryotic translation initiation factor 2 (eIF2?) at serine-51, a modification that leads to global inhibition of mRNA translation...
  18. Wang L, Ryoo H, Qi Y, Jasper H. PERK Limits Drosophila Lifespan by Promoting Intestinal Stem Cell Proliferation in Response to ER Stress. PLoS Genet. 2015;11:e1005220 pubmed publisher
    ..Our studies highlight the significance of the PERK branch of the unfolded protein response of the ER (UPRER) in intestinal homeostasis and provide a viable strategy to improve organismal health- and lifespan. ..
  19. Bjordal M, Arquier N, Kniazeff J, Pin J, Leopold P. Sensing of amino acids in a dopaminergic circuitry promotes rejection of an incomplete diet in Drosophila. Cell. 2014;156:510-21 pubmed publisher
    ..Taken together, these data identify a central amino-acid-sensing mechanism operating in specific DA neurons and controlling food intake. ..
  20. Santoyo J, Alcalde J, Mendez R, Pulido D, de Haro C. Cloning and characterization of a cDNA encoding a protein synthesis initiation factor-2alpha (eIF-2alpha) kinase from Drosophila melanogaster. Homology To yeast GCN2 protein kinase. J Biol Chem. 1997;272:12544-50 pubmed
  21. Kim K, Kim S, Kim J, Kim H, Yim J. Glutathione s-transferase omega 1 activity is sufficient to suppress neurodegeneration in a Drosophila model of Parkinson disease. J Biol Chem. 2012;287:6628-41 pubmed publisher
    ..Our results suggest a novel mechanism for the protective role of DmGSTO1 in parkin mutants, through the regulation of ATP synthase activity, and provide insight into potential therapies for Parkinson disease neurodegeneration. ..
  22. Matta B, Bitner Mathé B, Alves Ferreira M. Getting real with real-time qPCR: a case study of reference gene selection for morphological variation in Drosophila melanogaster wings. Dev Genes Evol. 2011;221:49-57 pubmed publisher
  23. Brown M, Chan M, Zimmerman J, Pack A, Jackson N, Naidoo N. Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis. Neurobiol Aging. 2014;35:1431-41 pubmed publisher
    ..Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge. ..
  24. Moore K, Plant J, Gaddam D, Craft J, Hollien J. Regulation of sumo mRNA during endoplasmic reticulum stress. PLoS ONE. 2013;8:e75723 pubmed publisher
    ..Unlike other RIDD targets, the sumo transcript does not stably associate with the ER membrane, but instead relies on an Xbp1-like stem loop and a second UPR mediator, Perk, for its degradation during stress. ..
  25. Katz M, Acevedo J, Loenarz C, Galagovsky D, Liu Yi P, Pérez Pepe M, et al. Sudestada1, a Drosophila ribosomal prolyl-hydroxylase required for mRNA translation, cell homeostasis, and organ growth. Proc Natl Acad Sci U S A. 2014;111:4025-30 pubmed publisher
    ..These observations, together with those on enzyme homologs described in the companion articles, reveal conserved biochemical and biological roles for a widely distributed ribosomal oxygenase. ..
  26. Satoh T, Ohba A, Liu Z, Inagaki T, Satoh A. dPob/EMC is essential for biosynthesis of rhodopsin and other multi-pass membrane proteins in Drosophila photoreceptors. elife. 2015;4: pubmed publisher
    ..These results collectively indicate that EMC is a key factor in the biogenesis of multi-pass transmembrane proteins, including Rh1, and its loss causes retinal degeneration. ..
  27. Lindsay H, Baines R, ffrench Constant R, Lilley K, Jacobs H, O Dell K. The dominant cold-sensitive Out-cold mutants of Drosophila melanogaster have novel missense mutations in the voltage-gated sodium channel gene paralytic. Genetics. 2008;180:873-84 pubmed publisher
    ..SNP mapping reduced the Ocd critical region to <100 kb and to six candidate genes: hangover, CG9947, CG4420, eIF2a, Rbp2, and paralytic (para)...
  28. Ryoo H. Drosophila as a model for unfolded protein response research. BMB Rep. 2015;48:445-53 pubmed
    ..The fact that the basic UPR pathways are conserved, together with the availability of many human disease models in this organism, makes Drosophila a powerful tool for studying human disease mechanisms. ..
  29. Qu S, Cavener D. Isolation and characterization of the Drosophila melanogaster eIF-2 alpha gene encoding the alpha subunit of translation initiation factor eIF-2. Gene. 1994;140:239-42 pubmed
    ..The D. melanogaster eIF-2 alpha mRNA is 1350 nt in length and is expressed throughout development. ..
  30. Stanewsky R, Rendahl K, Dill M, Saumweber H. Genetic and molecular analysis of the X chromosomal region 14B17-14C4 in Drosophila melanogaster: loss of function in NONA, a nuclear protein common to many cell types, results in specific physiological and behavioral defects. Genetics. 1993;135:419-42 pubmed
    ..Surviving males show more extreme defects in nervous system function than have been described for the hypomorphic alleles. Five other essential genes that reside within this region have been partially characterized. ..
  31. Penney J, Tsurudome K, Liao E, Elazzouzi F, Livingstone M, González M, et al. TOR is required for the retrograde regulation of synaptic homeostasis at the Drosophila neuromuscular junction. Neuron. 2012;74:166-78 pubmed publisher
    ..Our findings suggest that cap-dependent translation under the control of TOR plays a critical role in establishing the activity dependent homeostatic response at the NMJ. ..