HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex
| Autor: | Yan Wang, Jun Zhang, Jun-Ling Meng, Yu Zhang, Yu Pan, Juan Cai, Yu Zhou, Xiao-Ping Qian, He-Ting Mao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
TRAF3 Ubiquitin-Protein Ligases Polynucleotides lcsh:QR1-502 Virus Replication Sendai virus Article HACE1 lcsh:Microbiology Cell Line Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Ubiquitin Interferon Virology medicine Humans MAVS interferon inflammation Adaptor Proteins Signal Transducing TNF Receptor-Associated Factor 3 biology Interferon-beta biology.organism_classification Ubiquitin ligase Cell biology Poly I-C 030104 developmental biology Infectious Diseases 030220 oncology & carcinogenesis biology.protein Protein Multimerization Signal transduction Signal Transduction medicine.drug |
| Zdroj: | Viruses Viruses, Vol 8, Iss 5, p 146 (2016) Viruses; Volume 8; Issue 5; Pages: 146 |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v8050146 |
| Popis: | During virus infection, the cascade signaling pathway that leads to the production of proinflammatory cytokines is controlled at multiple levels to avoid detrimental overreaction. HACE1 has been characterized as an important tumor suppressor. Here, we identified HACE1 as an important negative regulator of virus-triggered type I IFN signaling. Overexpression of HACE1 inhibited Sendai virus- or poly (I:C)-induced signaling and resulted in reduced IFNB1 production and enhanced virus replication. Knockdown of HACE1 expression exhibited the opposite effects. Ubiquitin E3 ligase activity of the dead mutant HACE1/C876A had a comparable inhibitory function as WT HACE1, suggesting that the suppressive function of HACE1 on virus-induced signaling is independent of its E3 ligase activity. Further study indicated that HACE1 acted downstream of MAVS and upstream of TBK1. Mechanistic studies showed that HACE1 exerts its inhibitory role on virus-induced signaling by disrupting the MAVS-TRAF3 complex. Therefore, we uncovered a novel function of HACE1 in innate immunity regulation. |
| Databáze: | OpenAIRE |
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