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 - PubMed (original) (raw)

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

C R Vazquez de Aldana et al. Proc Natl Acad Sci U S A. 1993.

Abstract

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.

PubMed Disclaimer

References

    1. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 - PubMed
    1. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5350-4 - PubMed
    1. Mol Cell Biol. 1984 Jul;4(7):1326-33 - PubMed
    1. J Biol Chem. 1987 Jan 25;262(3):1206-12 - PubMed
    1. Methods Enzymol. 1987;154:164-75 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources