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Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90
The molecular chaperone heat shock protein 90 (Hsp90) and the co-chaperone/ubiquitin ligase carboxyl terminus of Hsc70-interacting protein (CHIP) control the turnover of client proteins. How this system decides to stabilize or degrade the client proteins under particular physiological or pathologica...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989103/ https://www.ncbi.nlm.nih.gov/pubmed/20924358 http://dx.doi.org/10.1038/emboj.2010.245 |
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author | Yan, Shan Sun, Xuxu Xiang, Binggang Cang, Hui Kang, Xunlei Chen, Yuying Li, Hui Shi, Guiying Yeh, Edward T H Wang, Beilei Wang, Xiangrui Yi, Jing |
author_facet | Yan, Shan Sun, Xuxu Xiang, Binggang Cang, Hui Kang, Xunlei Chen, Yuying Li, Hui Shi, Guiying Yeh, Edward T H Wang, Beilei Wang, Xiangrui Yi, Jing |
author_sort | Yan, Shan |
collection | PubMed |
description | The molecular chaperone heat shock protein 90 (Hsp90) and the co-chaperone/ubiquitin ligase carboxyl terminus of Hsc70-interacting protein (CHIP) control the turnover of client proteins. How this system decides to stabilize or degrade the client proteins under particular physiological or pathological conditions is unclear. We report here a novel client protein, the SUMO2/3 protease SENP3, that is sophisticatedly regulated by CHIP and Hsp90. SENP3 is maintained at a low basal level under non-stress condition due to Hsp90-independent CHIP-mediated ubiquitination. Upon mild oxidative stress, SENP3 undergoes thiol modification, which recruits Hsp90. Hsp90/SENP3 association protects SENP3 from CHIP-mediated ubiquitination and subsequent degradation, but this effect of Hsp90 requires the presence of CHIP. Our data demonstrate for the first time that CHIP and Hsp90 interplay with a client alternately under non-stress and stress conditions, and the choice between stabilization and degradation is made by the redox state of the client. In addition, enhanced SENP3/Hsp90 association is found in cancer. These findings provide new mechanistic insight into how cells regulate the SUMO protease in response to oxidative stress. |
format | Text |
id | pubmed-2989103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-29891032010-12-23 Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90 Yan, Shan Sun, Xuxu Xiang, Binggang Cang, Hui Kang, Xunlei Chen, Yuying Li, Hui Shi, Guiying Yeh, Edward T H Wang, Beilei Wang, Xiangrui Yi, Jing EMBO J Article The molecular chaperone heat shock protein 90 (Hsp90) and the co-chaperone/ubiquitin ligase carboxyl terminus of Hsc70-interacting protein (CHIP) control the turnover of client proteins. How this system decides to stabilize or degrade the client proteins under particular physiological or pathological conditions is unclear. We report here a novel client protein, the SUMO2/3 protease SENP3, that is sophisticatedly regulated by CHIP and Hsp90. SENP3 is maintained at a low basal level under non-stress condition due to Hsp90-independent CHIP-mediated ubiquitination. Upon mild oxidative stress, SENP3 undergoes thiol modification, which recruits Hsp90. Hsp90/SENP3 association protects SENP3 from CHIP-mediated ubiquitination and subsequent degradation, but this effect of Hsp90 requires the presence of CHIP. Our data demonstrate for the first time that CHIP and Hsp90 interplay with a client alternately under non-stress and stress conditions, and the choice between stabilization and degradation is made by the redox state of the client. In addition, enhanced SENP3/Hsp90 association is found in cancer. These findings provide new mechanistic insight into how cells regulate the SUMO protease in response to oxidative stress. Nature Publishing Group 2010-11-17 2010-10-05 /pmc/articles/PMC2989103/ /pubmed/20924358 http://dx.doi.org/10.1038/emboj.2010.245 Text en Copyright © 2010, European Molecular Biology Organization http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission. |
spellingShingle | Article Yan, Shan Sun, Xuxu Xiang, Binggang Cang, Hui Kang, Xunlei Chen, Yuying Li, Hui Shi, Guiying Yeh, Edward T H Wang, Beilei Wang, Xiangrui Yi, Jing Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90 |
title | Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90 |
title_full | Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90 |
title_fullStr | Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90 |
title_full_unstemmed | Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90 |
title_short | Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90 |
title_sort | redox regulation of the stability of the sumo protease senp3 via interactions with chip and hsp90 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989103/ https://www.ncbi.nlm.nih.gov/pubmed/20924358 http://dx.doi.org/10.1038/emboj.2010.245 |
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