Mutations in the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) that overcome the inhibitory effect of eIF-2 alpha phosphorylation on translation initiation.

Phosphorylation of eIF-2 alpha in Saccharomyces cerevisiae by the protein kinase GCN2 leads to inhibition of general translation initiation and a specific increase in translation of GCN4 mRNA. We isolated mutations in the eIF-2 alpha structural gene that do not affect the growth rate of wild-type yeast but which suppress ...
the toxic effects of eIF-2 alpha hyperphosphorylation catalyzed by mutationally activated forms of GCN2. These eIF-2 alpha mutations also impair translational derepression of GCN4 in strains expressing wild-type GCN2 protein. All four mutations alter single amino acids within 40 residues of the phosphorylation site in eIF-2 alpha; however, three alleles do not decrease the level of eIF-2 alpha phosphorylation. We propose that these mutations alter the interaction between eIF-2 and its recycling factor eukaryotic translation initiation factor 2B (eIF-2B) in a way that diminishes the inhibitory effect of phosphorylated eIF-2 on the essential function of eIF-2B in translation initiation. These mutations may identify a region in eIF-2 alpha that participates directly in a physical interaction with the GCN3 subunit of eIF-2B.
Mesh Terms:
Amino Acid Sequence, Base Sequence, Eukaryotic Initiation Factor-2, Gene Expression Regulation, Fungal, Genes, Suppressor, Guanine Nucleotide Exchange Factors, Molecular Sequence Data, Oligodeoxyribonucleotides, Peptide Chain Initiation, Translational, Phosphorylation, Protein-Serine-Threonine Kinases, Proteins, Saccharomyces cerevisiae, Structure-Activity Relationship, eIF-2 Kinase
Proc. Natl. Acad. Sci. U.S.A.
Date: Aug. 01, 1993
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