The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

eIF-2alpha  -  eukaryotic translation Initiation Factor...

Drosophila melanogaster

Synonyms: CG9946, Dmel\CG9946, EIF-2alpha, Eif2alpha, Eukaryotic translation initiation factor 2 subunit 1, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of eIF-2alpha

 

High impact information on eIF-2alpha

  • In the initiation phase of eukaryotic translation, eIF5 stimulates the hydrolysis of GTP bound to eIF2 in the 40S ribosomal pre-initiation complex, and the resultant GDP on eIF2 is replaced with GTP by the complex nucleotide exchange factor, eIF2B [2].
  • Furthermore, we demonstrated that phosphorylation of eIF2alpha is impaired in both mutants [3].
  • Eukaryotic initiation factor (eIF) 2B catalyzes a key regulatory step in the initiation of mRNA translation. eIF2B is well characterized in mammals and in yeast, although little is known about it in other eukaryotes. eIF2B is a hetropentamer which mediates the exchange of GDP for GTP on eIF2 [4].
  • Affinity-purified antibodies, raised against a synthetic peptide based on the predicted DGCN2 sequence, specifically immunoprecipitated an eIF-2alpha kinase activity and recognized an approximately 175 kDa phosphoprotein in Western blots of Drosophila embryo extracts [5].
  • Phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF-2alpha) is one of the best-characterized mechanisms for downregulating protein synthesis in mammalian cells in response to various stress conditions [5].
 

Biological context of eIF-2alpha

  • DGCN2 contains all of the 12 catalytic subdomains characteristic of eukaryotic Ser/Thr protein kinases and the conserved sequence of eIF-2alpha kinases in subdomain V [5].
  • In contrast, flies bearing the alanine eIF-2alpha mutant (HA) displayed a fast growth phenotype and females were significantly larger than nontransgenic control sisters [1].
  • The expression of the eIF-2alpha mutant transgenes, under the transcriptional control of the hsp70 promoter, was induced at various times during development to assess the developmental and biochemical effects [1].
  • Complementation of Deltagcn2 in yeast by dGCN2 depends on the presence of the critical regulatory phosphorylation site (serine 51) of eIF-2alpha. dGCN2 is composed of 10 exons encoding a protein of 1589 amino acids. dGCN2 mRNA is expressed throughout Drosophila development and is particularly abundant at the earliest stages of embryogenesis [6].
  • A key transcription factor for eukaryotic initiation factor-2 alpha is strongly homologous to developmental transcription factors and may link metabolic genes to cellular growth and development [7].
 

Anatomical context of eIF-2alpha

  • When highly purified eIF-2 is used the rate of nucleotide exchange is greatly reduced by Mg2+ and this reduction is overcome by the guanine-nucleotide-exchange factor (GEF) of rabbit reticulocytes [8].
 

Associations of eIF-2alpha with chemical compounds

  • Flies bearing the aspartic acid eIF-2alpha mutant (HD) transgene displayed a slow growth phenotype and small body size [1].
  • Phosphorylation of the translation initiation factor eIF-2alpha downregulates protein synthesis by sequestering the guanylate exchange factor eIF-2B [1].
  • BeK does not show any significant homology in the NH(2) terminal regulatory domain, suggesting a distinct regulatory mechanism of this novel eIF-2alpha kinase [9].
  • The Mg2+ impairment of guanine nucleotide exchange is less severe when highly purified eIF-2 is incubated at a higher temperature (37 degrees C) and is not observed at any temperature if partially purified eIF-2 is used instead of the highly purified factor [8].
  • This GEF-dependent exchange is inhibited when Drosophila eIF-2 is either phosphorylated by the hemin-controlled inhibitor (HCI) of rabbit reticulocytes or treated with phosphatidylserine or a rabbit eIF-2 X phosphatidylserine complex [8].
 

Other interactions of eIF-2alpha

  • Furthermore, the stable complexes between wild-type DPERK and DPERK-K671R mutant were mediated through the N terminus of the proteins and exhibited an in vitro eIF2alpha kinase activity [10].
  • Heat shock effects on phosphorylation of protein synthesis initiation factor proteins eIF-4E and eIF-2 alpha in Drosophila [11].
 

Analytical, diagnostic and therapeutic context of eIF-2alpha

References

  1. Mutations at the Ser50 residue of translation factor eIF-2alpha dominantly affect developmental rate, body weight, and viability of Drosophila melanogaster. Qu, S., Perlaky, S.E., Organ, E.L., Crawford, D., Cavener, D.R. Gene Expr. (1997) [Pubmed]
  2. Conserved bipartite motifs in yeast eIF5 and eIF2Bepsilon, GTPase-activating and GDP-GTP exchange factors in translation initiation, mediate binding to their common substrate eIF2. Asano, K., Krishnamoorthy, T., Phan, L., Pavitt, G.D., Hinnebusch, A.G. EMBO J. (1999) [Pubmed]
  3. Budding yeast GCN1 binds the GI domain to activate the eIF2alpha kinase GCN2. Kubota, H., Ota, K., Sakaki, Y., Ito, T. J. Biol. Chem. (2001) [Pubmed]
  4. Characterization of the initiation factor eIF2B and its regulation in Drosophila melanogaster. Williams, D.D., Pavitt, G.D., Proud, C.G. J. Biol. Chem. (2001) [Pubmed]
  5. 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. Santoyo, J., Alcalde, J., Méndez, R., Pulido, D., de Haro, C. J. Biol. Chem. (1997) [Pubmed]
  6. Isolation of the gene encoding the Drosophila melanogaster homolog of the Saccharomyces cerevisiae GCN2 eIF-2alpha kinase. Olsen, D.S., Jordan, B., Chen, D., Wek, R.C., Cavener, D.R. Genetics (1998) [Pubmed]
  7. A key transcription factor for eukaryotic initiation factor-2 alpha is strongly homologous to developmental transcription factors and may link metabolic genes to cellular growth and development. Efiok, B.J., Chiorini, J.A., Safer, B. J. Biol. Chem. (1994) [Pubmed]
  8. Protein synthesis in Drosophila melanogaster embryos. Two mechanisms for guanine nucleotide exchange on eukaryotic initiation factor 2. Mateu, M.G., Sierra, J.M. Eur. J. Biochem. (1987) [Pubmed]
  9. Cloning and characterization of an eukaryotic initiation factor-2alpha kinase from the silkworm, Bombyx mori. Prasad, M.D., Han, S.J., Nagaraju, J., Lee, W.J., Brey, P.T. Biochim. Biophys. Acta (2003) [Pubmed]
  10. Functional characterization of Drosophila melanogaster PERK eukaryotic initiation factor 2alpha (eIF2alpha) kinase. Pomar, N., Berlanga, J.J., Campuzano, S., Hernández, G., Elías, M., de Haro, C. Eur. J. Biochem. (2003) [Pubmed]
  11. Heat shock effects on phosphorylation of protein synthesis initiation factor proteins eIF-4E and eIF-2 alpha in Drosophila. Duncan, R.F., Cavener, D.R., Qu, S. Biochemistry (1995) [Pubmed]
  12. The 90-kilodalton peptide of the heme-regulated eIF-2 alpha kinase has sequence similarity with the 90-kilodalton heat shock protein. Rose, D.W., Wettenhall, R.E., Kudlicki, W., Kramer, G., Hardesty, B. Biochemistry (1987) [Pubmed]
 
WikiGenes - Universities