Role of Gcn4 for adaptation to methylglyoxal in Saccharomyces cerevisiae: methylglyoxal attenuates protein synthesis through phosphorylation of eIF2alpha.
Methylglyoxal is a ubiquitous 2-oxoaldehyde derived from glycolysis. Although an endogenous metabolite, methylglyoxal at high concentrations has deleterious effects on cellular functions. Since pretreatment of Saccharomyces cerevisiae cells with methylglyoxal at a low concentration alleviates the toxicity of a subsequent lethal concentration of this 2-oxoaldehyde, proteins synthesized during treatment with methylglyoxal are necessary for adaptation to methylglyoxal. Nevertheless, here we show that methylglyoxal attenuates the rate of overall protein synthesis in S. cerevisiae. Phosphorylation of the alpha subunit of translation initiation factor 2 (eIF2alpha) is induced by several types of environmental stress, and subsequently, overall protein synthesis is reduced due to the impairment of the formation of a translation initiation complex. We found that methylglyoxal activates the protein kinase Gcn2 to phosphorylate eIF2alpha. The transcription factor Gcn4 is a master regulator of gene expression under conditions of amino acid starvation and some environmental stresses, the level of which is regulated by Gcn2. We found that adaptation to methylglyoxal was impaired in gcn4Delta cells, indicating the expression of certain genes regulated by Gcn4 to be important for the adaptive response to methylglyoxal.
Nomura
Wataru
W
Laboratory of Molecular Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
Maeta
Kazuhiro
K
Kita
Keiko
K
Izawa
Shingo
S
Inoue
Yoshiharu
Y
D000222:Adaptation, Physiological; D050976:Basic-Leucine Zipper Transcription Factors; D002374:Catalase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects; D011765:Pyruvaldehyde / Q000378:metabolism / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; C501391:GCN4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011765:Pyruvaldehyde; C108078:catalase I; D002374:Catalase