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Asp56 in actin is critical for the full activity of the amino acid starvation‐responsive kinase Gcn2
Author(s) -
Ramesh Rashmi,
Dautel Martina,
Lee Yongook,
Kim Yeonsoo,
Storey Kirsty,
Gottfried Susanne,
Goss Kinzy Terri,
Huh WonKi,
Sattlegger Evelyn
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14137
Subject(s) - saccharomyces cerevisiae , phosphorylation , amino acid , biochemistry , actin , biology , microbiology and biotechnology , mutant , kinase , protein kinase a , eif2 , translation (biology) , yeast , chemistry , messenger rna , gene
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 eIF2α, 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 eIF2α 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 eIF2α 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.