ArticleThe Journal of experimental medicine2020
USP22 promotes IRF3 nuclear translocation and antiviral responses by deubiquitinating the importin protein KPNA2.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 80 citations in OpenAlex.
- Loss of the USP22 deubiquitylase confers resistance to chemotherapy in small cell lung cancer.Nature communications · 2026Article
- Roles of ubiquitin‑specific peptidase 22 in cellular fate: From embryonic survival to tissue repair, inflammation and metabolism (Review).International journal of molecular medicine · 2026Review
- YWHAZ downregulated innate immune responses to RNA viruses by inhibiting the IRF3 signaling pathway.mSphere · 2026Article
- Cytoplasmic retention of IRF3 binding Vimentin competitively with ERK1/2 mitigates acute myeloid leukemia through TFEB nuclear translocation.Cell communication and signaling : CCS · 2026Article
- Foot-and-mouth disease virus VP4 interferes with host interferon response by targeting the nuclear translocation of interferon regulatory factor 3 (IRF3).Veterinary research · 2026Article
- DEAD-box helicase gcDDX56 disrupts IRF3 nuclear import complex and promotes nuclear IRF3 degradation for enhancing GCRV replication.Journal of virology · 2025Article
- The deubiquitination enzyme USP14 promotes the tumourigenesis of gastric cancer by enhancing c-MYC nuclear translocation through deubiquitination of KPNA2.Cell death & disease · 2025Article
- USP5-Rich Apoptotic Extracellular Vesicles Regulate Nucleus Pulposus Cells Apoptosis and DNA Damage Repair by Preventing E2F1 Proteasomal Degradation.Journal of extracellular vesicles · 2025Article
- KPNA2 promotes lung adenocarcinoma progression by inducing glycolysis-assisted MYC nuclear translocation.Cytotechnology · 2025Article
- The DCDC2/ENO1 axis promotes tumor progression and immune evasion in intrahepatic cholangiocarcinoma via activating FGL1-LAG3 checkpoint.Journal of experimental & clinical cancer research : CR · 2025Article
- Targeting USP22 to promote K63-linked ubiquitination and degradation of SARS-CoV-2 nucleocapsid protein.Journal of virology · 2025Article
- Identification of telomere maintenance-driven molecular subtypes in hepatocellular carcinoma: implications for prognosis and targeted therapy via KPNA2.Discover oncology · 2025Article
- Inhibition of SCFCommunications biology · 2025Article
- SARS-CoV-2 S protein disrupts the formation of ISGF3 complex through conserved S2 subunit to antagonize type I interferon response.Journal of virology · 2025Article
- Direct lysine dimethylation of IRF3 by the methyltransferase SMYD3 attenuates antiviral innate immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity.Emerging microbes & infections · 2024Article
- MERS-CoV-nsp5 expression in human epithelial BEAS 2b cells attenuates type I interferon production by inhibiting IRF3 nuclear translocation.Cellular and molecular life sciences : CMLS · 2024Article
- Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3.Journal of molecular cell biology · 2024Article
- KPNA2 promotes the progression of gastric cancer by regulating the alternative splicing of related genes.Scientific reports · 2024Article
- The African Swine Fever Virus Virulence Determinant DP96R Suppresses Type I IFN Production Targeting IRF3.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
USP22 is a cytoplasmic and nuclear deubiquitinating enzyme, and the functions of cytoplasmic USP22 are unclear. Here, we discovered that cytoplasmic USP22 promoted nuclear translocation of IRF3 by deubiquitianting and stabilizing KPNA2 after viral infection. Viral infection induced USP22-IRF3 association in the cytoplasm in a KPNA2-depedent manner, and knockdown or knockout of USP22 or KPNA2 impaired IRF3 nuclear translocation and expression of downstream genes after viral infection. Consistently, Cre-ER Usp22fl/fl or Lyz2-Cre Usp22fl/fl mice produced decreased levels of type I IFNs after viral infection and exhibited increased susceptibility to lethal viral infection compared with the respective control littermates. Mechanistically, USP22 deubiquitinated and stabilized KPNA2 after viral infection to facilitate efficient nuclear translocation of IRF3. Reconstitution of KPNA2 into USP22 knockout cells restored virus-triggered nuclear translocation of IRF3 and cellular antiviral responses. These findings define a previously unknown function of cytoplasmic USP22 and establish a mechanistic link between USP22 and IRF3 nuclear translocation that expands potential therapeutic strategies for infectious diseases.
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