ArticleThe Journal of experimental medicine2014
USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 174 citations in OpenAlex.
- USP21-mediated deubiquitylation stimulates NuMA recruitment to the cell cortex to promote mitotic spindle orientation.Cell death and differentiation · 2026Article
- USP21 drives immune evasion in colorectal cancer via deubiquitination and stabilization of β-catenin.Cellular & molecular immunology · 2026Article
- Integrating machine learning and spatial transcriptomics uncovers shared immunomodulatory deubiquitinases in MAFLD and HCC.Human genetics · 2026Article
- Polycomb repressive-deubiquitinase complex safeguards oocyte epigenome and female fertility by restraining Polycomb activity.Nature communications · 2026Article
- Sec8: a novel positive regulator of RIG-I in anti-RNA viral defense.Cell death & disease · 2026Article
- Interplay between pathogen-mediated immune evasion and innate immune negative regulation in gastrointestinal tumors.Frontiers in immunology · 2026Review
- TRIM29 inhibits PRRSV replication by targeting nsp11 for degradation.Journal of virology · 2025Article
- Article
- Targeting USP21 to inhibit abdominal aortic aneurysm progression by suppressing the phenotypic transition of vascular smooth muscle cells.Cell reports. Medicine · 2025Article
- miR-30a enhanced RIG-I-mediated type I interferon antiviral response by targeting USP14.Microbiology spectrum · 2025Article
- USP1 inhibits influenza A and B virus replication in MDCK cells by mediating RIG-I deubiquitination.Cellular and molecular life sciences : CMLS · 2025Article
- PWWP3A disrupts the assembly of VISA/MAVS signalosome to inhibit innate immune response against RNA viruses.Nature communications · 2025Article
- ORMDL3 restrains type I interferon signaling and anti-tumor immunity by promoting RIG-I degradation.eLife · 2025Article
- Catch me if you can: viral nucleic acids to host sensors.Frontiers in immunology · 2025Review
- Integrative and comprehensive pan-cancer analysis of ubiquitin specific peptidase 11 (Heliyon · 2024Article
- Multiple E3 ligases act as antiviral factors against SARS-CoV-2 via inducing the ubiquitination and degradation of ORF9b.Journal of virology · 2024Article
- circCD2AP promotes epithelial mesenchymal transition and stemness in bladder cancer by regulating FOXQ1/USP21 axis.iScience · 2024Article
- Host Factors Modulate Virus-Induced IFN Production via Pattern Recognition Receptors.Journal of inflammation research · 2024Review
- Innate immune responses to RNA: sensing and signaling.Frontiers in immunology · 2024Review
- Ubiquitin ligase enzymes and de-ubiquitinating enzymes regulate innate immunity in the TLR, NLR, RLR, and cGAS-STING pathways.Immunologic research · 2023Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
Lys63-linked polyubiquitination of RIG-I is essential in antiviral immune defense, yet the molecular mechanism that negatively regulates this critical step is poorly understood. Here, we report that USP21 acts as a novel negative regulator in antiviral responses through its ability to bind to and deubiquitinate RIG-I. Overexpression of USP21 inhibited RNA virus-induced RIG-I polyubiquitination and RIG-I-mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-α/β production, and antiviral responses in MEFs in response to RNA virus infection. USP21 also restricted antiviral responses in peritoneal macrophages (PMs) and bone marrow-derived dendritic cells (BMDCs). USP21-deficient mice spontaneously developed splenomegaly and were more resistant to VSV infection with elevated production of IFNs. Chimeric mice with USP21-deficient hematopoietic cells developed virus-induced splenomegaly and were more resistant to VSV infection. Functional comparison of three deubiquitinases (USP21, A20, and CYLD) demonstrated that USP21 acts as a bona fide RIG-I deubiquitinase to down-regulate antiviral response independent of the A20 ubiquitin-editing complex. Our studies identify a previously unrecognized role for USP21 in the negative regulation of antiviral response through deubiquitinating RIG-I.
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Registered trials
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.