PloS one, 2013-11, Vol.8 (11), p.e80976-e80976
2013
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- Autor(en) / Beteiligte
- Titel
- Ubiquitin-specific proteases 25 negatively regulates virus-induced type I interferon signaling
- Ist Teil von
- PloS one, 2013-11, Vol.8 (11), p.e80976-e80976
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0080976Titel-ID: cdi_plos_journals_1459404235
- Format
- –
- Schlagworte
- Apoptosis, Biological response modifiers, Cell cycle, Cysteine, Cytokines, Enzymes, Gene Expression Regulation, Gene Silencing, Genes, Reporter, Genetic screening, HEK293 Cells, Histidine, Host-Pathogen Interactions, Humans, Interferon, Interferon regulatory factor 3, Interferon Regulatory Factor-3 - genetics, Interferon Regulatory Factor-3 - metabolism, Interferon-beta - genetics, Interferon-beta - metabolism, Kinases, Laboratories, Luciferases - genetics, Luciferases - metabolism, Lysine, Lysine - metabolism, Mutants, NF-κB protein, Phosphorylation, Plasmids, Proteases, Proteins, Receptors, Retinoic Acid - genetics, Receptors, Retinoic Acid - metabolism, Retinoic acid, RNA, Small Interfering - genetics, RNA, Small Interfering - metabolism, Sendai virus - genetics, Signal Transduction, Signaling, siRNA, TNF Receptor-Associated Factor 2 - genetics, TNF Receptor-Associated Factor 2 - metabolism, TNF Receptor-Associated Factor 6 - genetics, TNF Receptor-Associated Factor 6 - metabolism, TRAF2 protein, TRAF6 protein, Transcription Factor RelA - genetics, Transcription Factor RelA - metabolism, Tumor necrosis factor, Tumor necrosis factor-TNF, Ubiquitin, Ubiquitin Thiolesterase - antagonists & inhibitors, Ubiquitin Thiolesterase - genetics, Ubiquitin Thiolesterase - metabolism, Ubiquitination, Veterinary colleges, Veterinary medicine, Viral infections, Viruses