Asp56 in actin is critical for the full activity of the amino acid starvation-responsive kinase Gcn2.

Eukaryotes harbour a conserved signalling pathway, called General Amino Acid Control (GAAC) in Saccharomyces cerevisiae, for overcoming amino acid starvation. Upon starvation, the protein kinase Gcn2, which phosphorylates the eukaryotic translation initiation factor eIF2?, becomes stimulated to trigger the GAAC response. Genetic studies suggest that Yih1, which is the yeast ...
homolog of mammalian IMPACT and which binds monomeric actin, inhibits Gcn2 when released from actin. Here, we found that D56A substitution in actin (the act1-9 allele) leads to reduced eIF2? phosphorylation, suggesting that the Asp56 residue is required for full Gcn2 activation. In the act1-9 mutant, Yih1 overexpression further enhanced the sensitivity to amino acid starvation-inducing drugs and further impaired eIF2? phosphorylation, suggesting that Gcn2 inhibition was mediated via Yih1. The D56A substitution may impair the actin-Yih1 interaction, directly or indirectly, thereby increasing the amount of Yih1 available to inhibit Gcn2.
Mesh Terms:
Actins, Alanine, Alleles, Amino Acid Substitution, Aspartic Acid, Basic-Leucine Zipper Transcription Factors, Culture Media, Enzyme Inhibitors, Eukaryotic Initiation Factor-2, Gene Expression Regulation, Fungal, Genetic Complementation Test, Microfilament Proteins, Models, Molecular, Mutation, Phosphorylation, Protein Binding, Protein Conformation, Protein-Serine-Threonine Kinases, Recombinant Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Sulfonylurea Compounds
FEBS Lett
Date: Dec. 01, 2020
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