ArticleScientific reports2018
USP4 positively regulates RLR-induced NF-κB activation by targeting TRAF6 for K48-linked deubiquitination and inhibits enterovirus 71 replication.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- The deubiquitinase USP4 stabilizes the SCFNature communications · 2026Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- USP4 depletion-driven RAB7A ubiquitylation impairs autophagosome-lysosome fusion and aggravates periodontitis.Autophagy · 2025Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- USP26 suppresses type I interferon signaling by targeting TRAF3 for deubiquitination.PloS one · 2024Article
- Role of protein Post-translational modifications in enterovirus infection.Frontiers in microbiology · 2024Review
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- RNA modification in mRNA cancer vaccines.Clinical and experimental medicine · 2023Review
- TRAF3 activates STING-mediated suppression of EV-A71 and target of viral evasion.Signal transduction and targeted therapy · 2023Article
- Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors.International journal of molecular sciences · 2021Review
- The Ubiquitin Proteasome System and Skin Fibrosis.Molecular diagnosis & therapy · 2021Review
- Spotlight on USP4: Structure, Function, and Regulation.Frontiers in cell and developmental biology · 2021Review
- The Functional Deubiquitinating Enzymes in Control of Innate Antiviral Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- An Integrated View of Deubiquitinating Enzymes Involved in Type I Interferon Signaling, Host Defense and Antiviral Activities.Frontiers in immunology · 2021Review
- Importance of Deubiquitination in Macrophage-Mediated Viral Response and Inflammation.International journal of molecular sciences · 2020Review
- USP4 function and multifaceted roles in cancer: a possible and potential therapeutic target.Cancer cell international · 2020Review
- The Evolving Role of TRAFs in Mediating Inflammatory Responses.Frontiers in immunology · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinoic acid-inducible gene I-like receptor (RLR) is one of the most important pattern recognition receptors of the innate immune system that detects positive and/or negative stranded RNA viruses. Subsequently, it stimulates downstream transcription of interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB) inducing the production of interferons (IFNs) and inflammatory cytokines. Tumour necrosis factor receptor associated factor 6 (TRAF6) is a key protein involved in the RLR-mediated antiviral signalling pathway, recruiting additional proteins to form a multiprotein complex capable of activating the NF-κB inflammatory pathway. Despite TRAF6 playing an important role in regulating host immunity and viral infection, the deubiquitination of TRAF6 induced by viral infection remains elusive. In this study, we found that enterovirus 71 (EV71) infection attenuated the expression of Ubiquitin-specific protease 4 (USP4) in vitro and in vivo, while overexpression of USP4 significantly suppressed EV71 replication. Furthermore, it was found that EV71 infection reduced the RLR signalling pathway and enhanced the degradation of TRAF6. USP4 was also found to interact with TRAF6 and positively regulate the RLR-induced NF-κB signalling pathway, inhibiting the replication of EV71. Therefore, as a novel positive regulator of TRAF6, USP4 plays an essential role in EV71 infection by deubiquitinating K48-linked ubiquitin chains.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.