The protein kinase Gcn2p mediates sodium toxicity in yeast.
Phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2alpha) is a conserved mechanism regulating protein synthesis in response to various stresses. A screening for negative factors in yeast salt stress tolerance has led to the identification of Gcn2p, the single yeast eIF2alpha kinase that is activated by amino acid starvation in the general amino acid control response. Mutation of other components of this regulatory circuit such as GCN1 and GCN3 also resulted in improved NaCl tolerance. The gcn2 phenotype was not accompanied by changes in sodium or potassium homeostasis. NaCl induced a Gcn2p-dependent phosphorylation of eIF2alpha and translational activation of Gcn4p, the transcription factor that mediates the general amino acid control response. Mutations that activate Gcn4p function, such as gcd7-201, cpc2, and deletion of the translational regulatory region of the GCN4 gene, also cause salt sensitivity. It can be postulated that sodium activation of the Gcn2p pathway has toxic effects on growth under NaCl stress and that this novel mechanism of sodium toxicity may be of general significance in eukaryotes.
Goossens
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Instituto de Biologia Molecular y Celular de Plantas, Universidad Politécnica de Valencia-C.S.I.C., Camino de Vera s/n, 46022 Valencia, Spain.
Dever
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Pascual-Ahuir
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Serrano
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D000596:Amino Acids / Q000494:pharmacology; D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D020717:Eukaryotic Initiation Factor-2B; D005656:Fungal Proteins / Q000502:physiology; D009708:Nucleotidases / Q000235:genetics; D010445:Peptide Elongation Factors; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine / Q000378:metabolism; D012964:Sodium / Q000633:toxicity*
D000596:Amino Acids; D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; D020717:Eukaryotic Initiation Factor-2B; D005656:Fungal Proteins; C501389:GCN1 protein, S cerevisiae; C501390:GCN3 protein, S cerevisiae; D010445:Peptide Elongation Factors; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D012964:Sodium; D011494:Protein Kinases; C512912:GCN2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D009708:Nucleotidases; C053354:bisphosphoadenylate 3'-nucleotidase