HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1.
RIG-I like receptors (RLRs) recognize cytosolic viral RNA and initiate innate immunity; they increase the production of type I interferon (IFN) and the transcription of a series of antiviral genes to protect the host organism. Accurate regulation of the RLR pathway is important for avoiding tissue i...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-04-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3999155?pdf=render |
| _version_ | 1819261317539692544 |
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| author | Yanyan Peng Ruidan Xu Xiaofeng Zheng |
| author_facet | Yanyan Peng Ruidan Xu Xiaofeng Zheng |
| author_sort | Yanyan Peng |
| collection | DOAJ |
| description | RIG-I like receptors (RLRs) recognize cytosolic viral RNA and initiate innate immunity; they increase the production of type I interferon (IFN) and the transcription of a series of antiviral genes to protect the host organism. Accurate regulation of the RLR pathway is important for avoiding tissue injury induced by excessive immune response. HSCARG is a newly reported negative regulator of NF-κB. Here we demonstrated that HSCARG participates in innate immunity. HSCARG inhibited the cellular antiviral response in an NF-κB independent manner, whereas deficiency of HSCARG had an opposite effect. After viral infection, HSCARG interacted with tumor necrosis receptor-associated factor 3 (TRAF3) and inhibited its ubiquitination by promoting the recruitment of OTUB1 to TRAF3. Knockout of HSCARG attenuated the de-ubiquitination of TRAF3 by OTUB1, and knockdown of OTUB1 abolished the effect of HSCARG. HSCARG also interacted with Ikappa-B kinase epsilon (IKKε) after viral infection and impaired the association between TRAF3 and IKKε, which further decreased the phosphorylation of IKKε and interferon response factor 3 (IRF3), thus suppressed the dimerization and nuclear translocation of IRF3. Moreover, knockdown of TRAF3 dampened the inhibitory effect of IFN-β transcription by HSCARG, suggesting that TRAF3 is necessary for HSCARG to down-regulate RLR pathway. This study demonstrated that HSCARG is a negative regulator that enables balanced antiviral innate immunity. |
| first_indexed | 2024-12-23T19:39:53Z |
| format | Article |
| id | doaj.art-5d81991084794923801cdddc3b13bfb2 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-23T19:39:53Z |
| publishDate | 2014-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-5d81991084794923801cdddc3b13bfb22022-12-21T17:33:41ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-04-01104e100404110.1371/journal.ppat.1004041HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1.Yanyan PengRuidan XuXiaofeng ZhengRIG-I like receptors (RLRs) recognize cytosolic viral RNA and initiate innate immunity; they increase the production of type I interferon (IFN) and the transcription of a series of antiviral genes to protect the host organism. Accurate regulation of the RLR pathway is important for avoiding tissue injury induced by excessive immune response. HSCARG is a newly reported negative regulator of NF-κB. Here we demonstrated that HSCARG participates in innate immunity. HSCARG inhibited the cellular antiviral response in an NF-κB independent manner, whereas deficiency of HSCARG had an opposite effect. After viral infection, HSCARG interacted with tumor necrosis receptor-associated factor 3 (TRAF3) and inhibited its ubiquitination by promoting the recruitment of OTUB1 to TRAF3. Knockout of HSCARG attenuated the de-ubiquitination of TRAF3 by OTUB1, and knockdown of OTUB1 abolished the effect of HSCARG. HSCARG also interacted with Ikappa-B kinase epsilon (IKKε) after viral infection and impaired the association between TRAF3 and IKKε, which further decreased the phosphorylation of IKKε and interferon response factor 3 (IRF3), thus suppressed the dimerization and nuclear translocation of IRF3. Moreover, knockdown of TRAF3 dampened the inhibitory effect of IFN-β transcription by HSCARG, suggesting that TRAF3 is necessary for HSCARG to down-regulate RLR pathway. This study demonstrated that HSCARG is a negative regulator that enables balanced antiviral innate immunity.http://europepmc.org/articles/PMC3999155?pdf=render |
| spellingShingle | Yanyan Peng Ruidan Xu Xiaofeng Zheng HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1. PLoS Pathogens |
| title | HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1. |
| title_full | HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1. |
| title_fullStr | HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1. |
| title_full_unstemmed | HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1. |
| title_short | HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1. |
| title_sort | hscarg negatively regulates the cellular antiviral rig i like receptor signaling pathway by inhibiting traf3 ubiquitination via recruiting otub1 |
| url | http://europepmc.org/articles/PMC3999155?pdf=render |
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