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Ubiquitin-Specific Proteases 25 Negatively Regulates Virus-Induced Type I Interferon Signaling
Ubiquitination and deubiquitination have emerged as critical regulatory processes in the virus-triggered type I interferon (IFN) induction pathway. In this study, we carried out a targeted siRNA screen of 54 ubiquitin-specific proteases (USPs) and identified USP25 as a negative regulator of the viru...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832446/ https://www.ncbi.nlm.nih.gov/pubmed/24260525 http://dx.doi.org/10.1371/journal.pone.0080976 |
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author | Zhong, Huijuan Wang, Dang Fang, Liurong Zhang, Huan Luo, Rui Shang, Min Ouyang, Chao Ouyang, Haiping Chen, Huanchun Xiao, Shaobo |
author_facet | Zhong, Huijuan Wang, Dang Fang, Liurong Zhang, Huan Luo, Rui Shang, Min Ouyang, Chao Ouyang, Haiping Chen, Huanchun Xiao, Shaobo |
author_sort | Zhong, Huijuan |
collection | PubMed |
description | Ubiquitination and deubiquitination have emerged as critical regulatory processes in the virus-triggered type I interferon (IFN) induction pathway. In this study, we carried out a targeted siRNA screen of 54 ubiquitin-specific proteases (USPs) and identified USP25 as a negative regulator of the virus-triggered type I IFN signaling pathway. Overexpression of USP25 inhibited virus-induced activation of IFN-β, interferon regulation factor 3 (IRF3) and nuclear factor-kappa B (NF-κB), as well as the phosphorylation of IRF3 and NF-κB subunit p65. Furthermore, Knockdown of USP25 potentiated virus-induced induction of the IFN-β. In addition, detailed analysis demonstrated that USP25 cleaved lysine 48- and lysine 63-linked polyubiquitin chains in vitro and in vivo, and its deubiquitinating enzyme (DUB) activity, were dependent on a cysteine residue (Cys178) and a histidine residue (His607). USP25 mutants lacking DUB activity lost the ability to block virus-induced type I IFN to some degree. Mechanistically, USP25 deubiquitinated retinoic acid-inducible gene I (RIG-I), tumornecrosis factor (TNF) receptor-associated factor 2 (TRAF2), and TRAF6 to inhibit RIG-I-like receptor-mediated IFN signaling. Our findings suggest that USP25 is a novel DUB negatively regulating virus-induced type I IFN production. |
format | Online Article Text |
id | pubmed-3832446 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38324462013-11-20 Ubiquitin-Specific Proteases 25 Negatively Regulates Virus-Induced Type I Interferon Signaling Zhong, Huijuan Wang, Dang Fang, Liurong Zhang, Huan Luo, Rui Shang, Min Ouyang, Chao Ouyang, Haiping Chen, Huanchun Xiao, Shaobo PLoS One Research Article Ubiquitination and deubiquitination have emerged as critical regulatory processes in the virus-triggered type I interferon (IFN) induction pathway. In this study, we carried out a targeted siRNA screen of 54 ubiquitin-specific proteases (USPs) and identified USP25 as a negative regulator of the virus-triggered type I IFN signaling pathway. Overexpression of USP25 inhibited virus-induced activation of IFN-β, interferon regulation factor 3 (IRF3) and nuclear factor-kappa B (NF-κB), as well as the phosphorylation of IRF3 and NF-κB subunit p65. Furthermore, Knockdown of USP25 potentiated virus-induced induction of the IFN-β. In addition, detailed analysis demonstrated that USP25 cleaved lysine 48- and lysine 63-linked polyubiquitin chains in vitro and in vivo, and its deubiquitinating enzyme (DUB) activity, were dependent on a cysteine residue (Cys178) and a histidine residue (His607). USP25 mutants lacking DUB activity lost the ability to block virus-induced type I IFN to some degree. Mechanistically, USP25 deubiquitinated retinoic acid-inducible gene I (RIG-I), tumornecrosis factor (TNF) receptor-associated factor 2 (TRAF2), and TRAF6 to inhibit RIG-I-like receptor-mediated IFN signaling. Our findings suggest that USP25 is a novel DUB negatively regulating virus-induced type I IFN production. Public Library of Science 2013-11-18 /pmc/articles/PMC3832446/ /pubmed/24260525 http://dx.doi.org/10.1371/journal.pone.0080976 Text en © 2013 Zhong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhong, Huijuan Wang, Dang Fang, Liurong Zhang, Huan Luo, Rui Shang, Min Ouyang, Chao Ouyang, Haiping Chen, Huanchun Xiao, Shaobo Ubiquitin-Specific Proteases 25 Negatively Regulates Virus-Induced Type I Interferon Signaling |
title | Ubiquitin-Specific Proteases 25 Negatively Regulates Virus-Induced Type I Interferon Signaling |
title_full | Ubiquitin-Specific Proteases 25 Negatively Regulates Virus-Induced Type I Interferon Signaling |
title_fullStr | Ubiquitin-Specific Proteases 25 Negatively Regulates Virus-Induced Type I Interferon Signaling |
title_full_unstemmed | Ubiquitin-Specific Proteases 25 Negatively Regulates Virus-Induced Type I Interferon Signaling |
title_short | Ubiquitin-Specific Proteases 25 Negatively Regulates Virus-Induced Type I Interferon Signaling |
title_sort | ubiquitin-specific proteases 25 negatively regulates virus-induced type i interferon signaling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832446/ https://www.ncbi.nlm.nih.gov/pubmed/24260525 http://dx.doi.org/10.1371/journal.pone.0080976 |
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