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Large G3BP-induced granules trigger eIF2α phosphorylation
Stress granules are large messenger ribonucleoprotein (mRNP) aggregates composed of translation initiation factors and mRNAs that appear when the cell encounters various stressors. Current dogma indicates that stress granules function as inert storage depots for translationally silenced mRNPs until...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442399/ https://www.ncbi.nlm.nih.gov/pubmed/22833567 http://dx.doi.org/10.1091/mbc.E12-05-0385 |
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author | Reineke, Lucas C. Dougherty, Jon D. Pierre, Philippe Lloyd, Richard E. |
author_facet | Reineke, Lucas C. Dougherty, Jon D. Pierre, Philippe Lloyd, Richard E. |
author_sort | Reineke, Lucas C. |
collection | PubMed |
description | Stress granules are large messenger ribonucleoprotein (mRNP) aggregates composed of translation initiation factors and mRNAs that appear when the cell encounters various stressors. Current dogma indicates that stress granules function as inert storage depots for translationally silenced mRNPs until the cell signals for renewed translation and stress granule disassembly. We used RasGAP SH3-binding protein (G3BP) overexpression to induce stress granules and study their assembly process and signaling to the translation apparatus. We found that assembly of large G3BP-induced stress granules, but not small granules, precedes phosphorylation of eIF2α. Using mouse embryonic fibroblasts depleted for individual eukaryotic initiation factor 2α (eIF2α) kinases, we identified protein kinase R as the principal kinase that mediates eIF2α phosphorylation by large G3BP-induced granules. These data indicate that increasing stress granule size is associated with a threshold or switch that must be triggered in order for eIF2α phosphorylation and subsequent translational repression to occur. Furthermore, these data suggest that stress granules are active in signaling to the translational machinery and may be important regulators of the innate immune response. |
format | Online Article Text |
id | pubmed-3442399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-34423992012-11-30 Large G3BP-induced granules trigger eIF2α phosphorylation Reineke, Lucas C. Dougherty, Jon D. Pierre, Philippe Lloyd, Richard E. Mol Biol Cell Articles Stress granules are large messenger ribonucleoprotein (mRNP) aggregates composed of translation initiation factors and mRNAs that appear when the cell encounters various stressors. Current dogma indicates that stress granules function as inert storage depots for translationally silenced mRNPs until the cell signals for renewed translation and stress granule disassembly. We used RasGAP SH3-binding protein (G3BP) overexpression to induce stress granules and study their assembly process and signaling to the translation apparatus. We found that assembly of large G3BP-induced stress granules, but not small granules, precedes phosphorylation of eIF2α. Using mouse embryonic fibroblasts depleted for individual eukaryotic initiation factor 2α (eIF2α) kinases, we identified protein kinase R as the principal kinase that mediates eIF2α phosphorylation by large G3BP-induced granules. These data indicate that increasing stress granule size is associated with a threshold or switch that must be triggered in order for eIF2α phosphorylation and subsequent translational repression to occur. Furthermore, these data suggest that stress granules are active in signaling to the translational machinery and may be important regulators of the innate immune response. The American Society for Cell Biology 2012-09-15 /pmc/articles/PMC3442399/ /pubmed/22833567 http://dx.doi.org/10.1091/mbc.E12-05-0385 Text en © 2012 Reineke et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Reineke, Lucas C. Dougherty, Jon D. Pierre, Philippe Lloyd, Richard E. Large G3BP-induced granules trigger eIF2α phosphorylation |
title | Large G3BP-induced granules trigger eIF2α phosphorylation |
title_full | Large G3BP-induced granules trigger eIF2α phosphorylation |
title_fullStr | Large G3BP-induced granules trigger eIF2α phosphorylation |
title_full_unstemmed | Large G3BP-induced granules trigger eIF2α phosphorylation |
title_short | Large G3BP-induced granules trigger eIF2α phosphorylation |
title_sort | large g3bp-induced granules trigger eif2α phosphorylation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442399/ https://www.ncbi.nlm.nih.gov/pubmed/22833567 http://dx.doi.org/10.1091/mbc.E12-05-0385 |
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