Abstract
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.
Highlights
In the present work a genetic analysis has led to the identification of Gcn2p as a negative determinant of yeast salt tolerance
A Transposon Insertion into the GCN2 Locus Causes NaCl Tolerance—In order to identify novel determinants of salt tolerance in S. cerevisiae, we have designed a screening based on the isolation of recessive, loss-of-function mutations suppressing the salt sensitivity of ena1– 4 disruptants in medium supplemented with methionine
High Salinity Induces the General Amino Acid Control Response—In the present study, a genetic screening for negative determinants of yeast salt tolerance has led to the following discoveries. (i) High salinity induces the Gcn2p-mediated phosphorylation of eIF2␣ and thereby activates the translational control of GCN4. (ii) This response negatively affects salt tolerance
Summary
In the present work a genetic analysis has led to the identification of Gcn2p as a negative determinant of yeast salt tolerance This protein kinase participates in one of the best characterized mechanisms of translational regulation in eukaryotes, which involves the phosphorylation of the ␣subunit of eukaryotic initiation factor 2 (eIF2␣) at serine 51 [10, 11]. In yeast this regulatory pathway is activated when cells are subjected to amino acid or purine starvation and is called the general amino acid control [12].
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