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Stress-induced NEDDylation promotes cytosolic protein aggregation through HDAC6 in a p62-dependent manner
Stress-coupled NEDDylation potentially regulates the aggregation of nuclear proteins, which could protect the nuclear ubiquitin-proteasome system from proteotoxic stress. However, it remains unclear how NEDDylation controls protein-aggregation responses to diverse stress conditions. Here, we identif...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903351/ https://www.ncbi.nlm.nih.gov/pubmed/33665565 http://dx.doi.org/10.1016/j.isci.2021.102146 |
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author | Kim, Soyeon Kwon, Mira Hwang, Yiseul Yoon, Junghyun Park, Sangwook Kang, Ho Chul |
author_facet | Kim, Soyeon Kwon, Mira Hwang, Yiseul Yoon, Junghyun Park, Sangwook Kang, Ho Chul |
author_sort | Kim, Soyeon |
collection | PubMed |
description | Stress-coupled NEDDylation potentially regulates the aggregation of nuclear proteins, which could protect the nuclear ubiquitin-proteasome system from proteotoxic stress. However, it remains unclear how NEDDylation controls protein-aggregation responses to diverse stress conditions. Here, we identified HDAC6 as a direct NEDD8-binding partner that regulates the formation of aggresome-like bodies (ALBs) containing NEDDylated cytosolic protein aggregates during ubiquitin stress. HDAC6 colocalizes with stress-induced ALBs, and HDAC6 inhibition suppresses ALBs formation, but not stress-induced NEDDylation, suggesting that HDAC6 carries NEDDylated-proteins to generate ALBs. Then, we monitored the ALBs-associated proteostasis network and found that p62 directly controls ALBs formation as an acceptor of NEDDylated cytosolic aggregates. Interestingly, we also observed that ALBs are highly condensed in chloroquine-treated cells with impaired autophagic flux, indicating that ALBs rely on autophagy. Collectively, our data suggest that NEDD8, HDAC6, and p62 are involved in the management of proteotoxic stress by forming cytosolic ALBs coupled to the aggresome-autophagy flux. |
format | Online Article Text |
id | pubmed-7903351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-79033512021-03-03 Stress-induced NEDDylation promotes cytosolic protein aggregation through HDAC6 in a p62-dependent manner Kim, Soyeon Kwon, Mira Hwang, Yiseul Yoon, Junghyun Park, Sangwook Kang, Ho Chul iScience Article Stress-coupled NEDDylation potentially regulates the aggregation of nuclear proteins, which could protect the nuclear ubiquitin-proteasome system from proteotoxic stress. However, it remains unclear how NEDDylation controls protein-aggregation responses to diverse stress conditions. Here, we identified HDAC6 as a direct NEDD8-binding partner that regulates the formation of aggresome-like bodies (ALBs) containing NEDDylated cytosolic protein aggregates during ubiquitin stress. HDAC6 colocalizes with stress-induced ALBs, and HDAC6 inhibition suppresses ALBs formation, but not stress-induced NEDDylation, suggesting that HDAC6 carries NEDDylated-proteins to generate ALBs. Then, we monitored the ALBs-associated proteostasis network and found that p62 directly controls ALBs formation as an acceptor of NEDDylated cytosolic aggregates. Interestingly, we also observed that ALBs are highly condensed in chloroquine-treated cells with impaired autophagic flux, indicating that ALBs rely on autophagy. Collectively, our data suggest that NEDD8, HDAC6, and p62 are involved in the management of proteotoxic stress by forming cytosolic ALBs coupled to the aggresome-autophagy flux. Elsevier 2021-02-06 /pmc/articles/PMC7903351/ /pubmed/33665565 http://dx.doi.org/10.1016/j.isci.2021.102146 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Kim, Soyeon Kwon, Mira Hwang, Yiseul Yoon, Junghyun Park, Sangwook Kang, Ho Chul Stress-induced NEDDylation promotes cytosolic protein aggregation through HDAC6 in a p62-dependent manner |
title | Stress-induced NEDDylation promotes cytosolic protein aggregation through HDAC6 in a p62-dependent manner |
title_full | Stress-induced NEDDylation promotes cytosolic protein aggregation through HDAC6 in a p62-dependent manner |
title_fullStr | Stress-induced NEDDylation promotes cytosolic protein aggregation through HDAC6 in a p62-dependent manner |
title_full_unstemmed | Stress-induced NEDDylation promotes cytosolic protein aggregation through HDAC6 in a p62-dependent manner |
title_short | Stress-induced NEDDylation promotes cytosolic protein aggregation through HDAC6 in a p62-dependent manner |
title_sort | stress-induced neddylation promotes cytosolic protein aggregation through hdac6 in a p62-dependent manner |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903351/ https://www.ncbi.nlm.nih.gov/pubmed/33665565 http://dx.doi.org/10.1016/j.isci.2021.102146 |
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