Absence of ataxin-3 leads to enhanced stress response in C. elegans.
Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein degradation by the ubiquitin-proteasome pathway. C. elegans and mouse ataxin-3 knockout models are v...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-04-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3079722?pdf=render |
| _version_ | 1828791779197976576 |
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| author | Ana João Rodrigues Andreia Neves-Carvalho Andreia Teixeira-Castro Anne Rokka Garry Corthals Elsa Logarinho Patrícia Maciel |
| author_facet | Ana João Rodrigues Andreia Neves-Carvalho Andreia Teixeira-Castro Anne Rokka Garry Corthals Elsa Logarinho Patrícia Maciel |
| author_sort | Ana João Rodrigues |
| collection | DOAJ |
| description | Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein degradation by the ubiquitin-proteasome pathway. C. elegans and mouse ataxin-3 knockout models are viable and without any obvious phenotype in a basal condition however their phenotype in stress situations has never been described.Considering the role of ataxin-3 in the protein degradation pathway, we analyzed the effects of heat shock, a known protein homeostasis stressor, in C. elegans ataxin-3 (ATX-3) knockout animals. We found that ATX-3 mutants have an exacerbated stress response and survive significantly better than wild type animals when subjected to a noxious heat shock stimulus. This increased thermotolerance of mutants was further enhanced by pre-exposure to a mild heat shock. At a molecular level, ATX-3 mutants have a distinct transcriptomic and proteomic profile with several molecular chaperones abnormally up-regulated during heat shock and recovery, consistent with the observed resistance phenotype.The improved thermotolerance in ATX-3 mutants is independent of heat shock factor 1, the maestro of the heat shock response, but fully dependent on DAF-16, a critical stress responsive transcription factor involved in longevity and stress resistance. We also show that the increased thermotolerance of ATX-3 mutants is mainly due to HSP-16.2, C12C8.1 and F44E5.5 given that the knockdown of these heat shock proteins using RNA interference causes the phenotype to revert. This report suggests that the absence of ATX-3 activates the DAF-16 pathway leading to an overexpression of molecular chaperones, which yields knockout animals with an improved capacity for dealing with deleterious stimuli. |
| first_indexed | 2024-12-12T02:56:53Z |
| format | Article |
| id | doaj.art-9a0fd5ae62ea4b98964b50f57fe31678 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T02:56:53Z |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9a0fd5ae62ea4b98964b50f57fe316782022-12-22T00:40:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1851210.1371/journal.pone.0018512Absence of ataxin-3 leads to enhanced stress response in C. elegans.Ana João RodriguesAndreia Neves-CarvalhoAndreia Teixeira-CastroAnne RokkaGarry CorthalsElsa LogarinhoPatrícia MacielAtaxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein degradation by the ubiquitin-proteasome pathway. C. elegans and mouse ataxin-3 knockout models are viable and without any obvious phenotype in a basal condition however their phenotype in stress situations has never been described.Considering the role of ataxin-3 in the protein degradation pathway, we analyzed the effects of heat shock, a known protein homeostasis stressor, in C. elegans ataxin-3 (ATX-3) knockout animals. We found that ATX-3 mutants have an exacerbated stress response and survive significantly better than wild type animals when subjected to a noxious heat shock stimulus. This increased thermotolerance of mutants was further enhanced by pre-exposure to a mild heat shock. At a molecular level, ATX-3 mutants have a distinct transcriptomic and proteomic profile with several molecular chaperones abnormally up-regulated during heat shock and recovery, consistent with the observed resistance phenotype.The improved thermotolerance in ATX-3 mutants is independent of heat shock factor 1, the maestro of the heat shock response, but fully dependent on DAF-16, a critical stress responsive transcription factor involved in longevity and stress resistance. We also show that the increased thermotolerance of ATX-3 mutants is mainly due to HSP-16.2, C12C8.1 and F44E5.5 given that the knockdown of these heat shock proteins using RNA interference causes the phenotype to revert. This report suggests that the absence of ATX-3 activates the DAF-16 pathway leading to an overexpression of molecular chaperones, which yields knockout animals with an improved capacity for dealing with deleterious stimuli.http://europepmc.org/articles/PMC3079722?pdf=render |
| spellingShingle | Ana João Rodrigues Andreia Neves-Carvalho Andreia Teixeira-Castro Anne Rokka Garry Corthals Elsa Logarinho Patrícia Maciel Absence of ataxin-3 leads to enhanced stress response in C. elegans. PLoS ONE |
| title | Absence of ataxin-3 leads to enhanced stress response in C. elegans. |
| title_full | Absence of ataxin-3 leads to enhanced stress response in C. elegans. |
| title_fullStr | Absence of ataxin-3 leads to enhanced stress response in C. elegans. |
| title_full_unstemmed | Absence of ataxin-3 leads to enhanced stress response in C. elegans. |
| title_short | Absence of ataxin-3 leads to enhanced stress response in C. elegans. |
| title_sort | absence of ataxin 3 leads to enhanced stress response in c elegans |
| url | http://europepmc.org/articles/PMC3079722?pdf=render |
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