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Reference - PMID:28771613 - Activation of Gcn2 in response to different stresses.

Reference summary

PubMed ID
PMID:28771613
Title
Activation of Gcn2 in response to different stresses.
Authors
Anda S, Zach R, Grallert B
Citation
PLoS One 2017;12(8):e0182143
Publication year
2017
Abstract
All organisms have evolved pathways to respond to different forms of cellular stress. The Gcn2 kinase is best known as a regulator of translation initiation in response to starvation for amino acids. Work in budding yeast has showed that the molecular mechanism of GCN2 activation involves the binding of uncharged tRNAs, which results in a conformational change and GCN2 activation. This pathway requires GCN1, which ensures delivery of the uncharged tRNA onto GCN2. However, Gcn2 is activated by a number of other stresses which do not obviously involve accumulation of uncharged tRNAs, raising the question how Gcn2 is activated under these conditions. Here we investigate the requirement for ongoing translation and tRNA binding for Gcn2 activation after different stresses in fission yeast. We find that mutating the tRNA-binding site on Gcn2 or deleting Gcn1 abolishes Gcn2 activation under all the investigated conditions. These results suggest that tRNA binding to Gcn2 is required for Gcn2 activation not only in response to starvation but also after UV irradiation and oxidative stress.

Annotation

GO biological process

GO:0031571 - mitotic G1 DNA damage checkpoint signaling

Genes:

GO:1904689 - negative regulation of cytoplasmic translational initiation

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GO molecular function

GO:0004694 - eukaryotic translation initiation factor 2alpha kinase activity

Genes:

GO:0030295 - protein kinase activator activity

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Modification

MOD:00696 - phosphorylated residue

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Single locus phenotype

FYPO:0005179 - abnormal mitotic cell cycle regulation during cellular response to UV during mitotic G1 phase

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Genotypes:

FYPO:0002898 - abolished protein phosphorylation during cellular response to DNA damage

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Genotypes:

FYPO:0006232 - abolished protein phosphorylation during cellular response to hydrogen peroxide

Genes:

Genotypes:

FYPO:0006398 - abolished protein phosphorylation during cellular response to leucine starvation

Genes:

Genotypes:

FYPO:0002177 - viable vegetative cell with normal cell morphology

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Genotypes: