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Activation of Gcn2 in response to different stresses

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 bindin...

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Detalles Bibliográficos
Autores principales: Anda, Silje, Zach, Róbert, Grallert, Beáta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542535/
https://www.ncbi.nlm.nih.gov/pubmed/28771613
http://dx.doi.org/10.1371/journal.pone.0182143
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author Anda, Silje
Zach, Róbert
Grallert, Beáta
author_facet Anda, Silje
Zach, Róbert
Grallert, Beáta
author_sort Anda, Silje
collection PubMed
description 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.
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spelling pubmed-55425352017-08-12 Activation of Gcn2 in response to different stresses Anda, Silje Zach, Róbert Grallert, Beáta PLoS One Research Article 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. Public Library of Science 2017-08-03 /pmc/articles/PMC5542535/ /pubmed/28771613 http://dx.doi.org/10.1371/journal.pone.0182143 Text en © 2017 Anda et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Anda, Silje
Zach, Róbert
Grallert, Beáta
Activation of Gcn2 in response to different stresses
title Activation of Gcn2 in response to different stresses
title_full Activation of Gcn2 in response to different stresses
title_fullStr Activation of Gcn2 in response to different stresses
title_full_unstemmed Activation of Gcn2 in response to different stresses
title_short Activation of Gcn2 in response to different stresses
title_sort activation of gcn2 in response to different stresses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542535/
https://www.ncbi.nlm.nih.gov/pubmed/28771613
http://dx.doi.org/10.1371/journal.pone.0182143
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