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NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation
During cell life, proteins often misfold, depending on particular mutations or environmental changes, which may lead to protein aggregates that are toxic for the cell. Such protein aggregates are the root cause of numerous diseases called “protein conformational diseases,” such as myofibrillar myopa...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884063/ https://www.ncbi.nlm.nih.gov/pubmed/27075172 http://dx.doi.org/10.1091/mbc.E15-12-0835 |
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author | Nivon, Mathieu Fort, Loïc Muller, Pascale Richet, Emma Simon, Stéphanie Guey, Baptiste Fournier, Maëlenn Arrigo, André-Patrick Hetz, Claudio Atkin, Julie D. Kretz-Remy, Carole |
author_facet | Nivon, Mathieu Fort, Loïc Muller, Pascale Richet, Emma Simon, Stéphanie Guey, Baptiste Fournier, Maëlenn Arrigo, André-Patrick Hetz, Claudio Atkin, Julie D. Kretz-Remy, Carole |
author_sort | Nivon, Mathieu |
collection | PubMed |
description | During cell life, proteins often misfold, depending on particular mutations or environmental changes, which may lead to protein aggregates that are toxic for the cell. Such protein aggregates are the root cause of numerous diseases called “protein conformational diseases,” such as myofibrillar myopathy and familial amyotrophic lateral sclerosis. To fight against aggregates, cells are equipped with protein quality control mechanisms. Here we report that NFκB transcription factor is activated by misincorporation of amino acid analogues into proteins, inhibition of proteasomal activity, expression of the R120G mutated form of HspB5 (associated with myofibrillar myopathy), or expression of the G985R and G93A mutated forms of superoxide dismutase 1 (linked to familial amyotrophic lateral sclerosis). This noncanonical stimulation of NFκB triggers the up-regulation of BAG3 and HspB8 expression, two activators of selective autophagy, which relocalize to protein aggregates. Then NFκB-dependent autophagy allows the clearance of protein aggregates. Thus NFκB appears as a central and major regulator of protein aggregate clearance by modulating autophagic activity. In this context, the pharmacological stimulation of this quality control pathway might represent a valuable strategy for therapies against protein conformational diseases. |
format | Online Article Text |
id | pubmed-4884063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-48840632016-08-16 NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation Nivon, Mathieu Fort, Loïc Muller, Pascale Richet, Emma Simon, Stéphanie Guey, Baptiste Fournier, Maëlenn Arrigo, André-Patrick Hetz, Claudio Atkin, Julie D. Kretz-Remy, Carole Mol Biol Cell Articles During cell life, proteins often misfold, depending on particular mutations or environmental changes, which may lead to protein aggregates that are toxic for the cell. Such protein aggregates are the root cause of numerous diseases called “protein conformational diseases,” such as myofibrillar myopathy and familial amyotrophic lateral sclerosis. To fight against aggregates, cells are equipped with protein quality control mechanisms. Here we report that NFκB transcription factor is activated by misincorporation of amino acid analogues into proteins, inhibition of proteasomal activity, expression of the R120G mutated form of HspB5 (associated with myofibrillar myopathy), or expression of the G985R and G93A mutated forms of superoxide dismutase 1 (linked to familial amyotrophic lateral sclerosis). This noncanonical stimulation of NFκB triggers the up-regulation of BAG3 and HspB8 expression, two activators of selective autophagy, which relocalize to protein aggregates. Then NFκB-dependent autophagy allows the clearance of protein aggregates. Thus NFκB appears as a central and major regulator of protein aggregate clearance by modulating autophagic activity. In this context, the pharmacological stimulation of this quality control pathway might represent a valuable strategy for therapies against protein conformational diseases. The American Society for Cell Biology 2016-06-01 /pmc/articles/PMC4884063/ /pubmed/27075172 http://dx.doi.org/10.1091/mbc.E15-12-0835 Text en © 2016 Nivon 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 for Cell Biology. |
spellingShingle | Articles Nivon, Mathieu Fort, Loïc Muller, Pascale Richet, Emma Simon, Stéphanie Guey, Baptiste Fournier, Maëlenn Arrigo, André-Patrick Hetz, Claudio Atkin, Julie D. Kretz-Remy, Carole NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation |
title | NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation |
title_full | NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation |
title_fullStr | NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation |
title_full_unstemmed | NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation |
title_short | NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation |
title_sort | nfκb is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884063/ https://www.ncbi.nlm.nih.gov/pubmed/27075172 http://dx.doi.org/10.1091/mbc.E15-12-0835 |
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