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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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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. |
format | Online Article Text |
id | pubmed-5542535 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT andasilje activationofgcn2inresponsetodifferentstresses AT zachrobert activationofgcn2inresponsetodifferentstresses AT grallertbeata activationofgcn2inresponsetodifferentstresses |