ArticlePLoS pathogens2023
USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.
Article in PLoS pathogens, 2023. 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 12 papers.
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Who cites it
12 citing papers in PubMed.
- FAM135B Deficiency Inhibits Cytotoxic T-cell Activity in Triple-Negative Breast Cancer by Blocking the IFI16-Dependent STING Pathway.Cancer immunology research · 2026Article
- Targeting macrophage-derived SPP1 enhances CD8 T cell infiltration via ROS-DNA fragment/cGAS-STING/STAT1-mediated CXCL9/10 in tumor microenvironment.Journal for immunotherapy of cancer · 2026Article
- ZBP1 and IFI16: novel innate sensors and inflammation regulation under infection stress.Frontiers in immunology · 2026Review
- The USP43/RNF2 axis negatively regulates antiviral innate immunity by promoting TBK1 ubiquitination and degradation.Cell death and differentiation · 2025Article
- IRF6 Enhances IFN-β Expression and Inhibits Viral Replication to Reduce the Severity of Herpetic Stromal Keratitis.Journal of inflammation research · 2025Article
- Tug of war: innate immunity and herpes simplex keratitis.Frontiers in immunology · 2025Review
- An updated review of HSV-1 infection-associated diseases and treatment, vaccine development, and vector therapy application.Virulence · 2024Review
- The battle between host antiviral innate immunity and immune evasion by cytomegalovirus.Cellular and molecular life sciences : CMLS · 2024Review
- RNF213 promotes Treg cell differentiation by facilitating K63-linked ubiquitination and nuclear translocation of FOXO1.Nature communications · 2024Article
- IFI16 promotes the progression of clear cell renal cell carcinoma through the IL6/PI3K/AKT axis.Journal of translational medicine · 2024Article
- Correction: USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.PLoS pathogens · 2023Article
- Spotlights on ubiquitin-specific protease 12 (USP12) in diseases: from multifaceted roles to pathophysiological mechanisms.Journal of translational medicine · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deubiquitinating enzymes (DUBs) regulate antiviral immune response through targeting DNA sensor signaling pathway members. As one of the DNA sensors, interferon (IFN)-γ inducible protein 16 (IFI16) play a major role in response to virus infections through activating the canonical STING/TBK-1/IRF3 signaling pathway. Only a few studies discuss the function of DUBs in IFI16-mediated antiviral response. Ubiquitin-specific protease 12 (USP12), which is one of the major members of the USP family, participates in various biological functions. However, whether USP12 regulates the nucleic acid sensor to modulate antiviral immune responses has not yet been elucidated. In this study, we found that knockout or knockdown of USP12 impaired the HSV-1-induced expressions of IFN-β, CCL-5, IL-6, and downstream interferon-stimulated genes (ISGs). Moreover, USP12 deficiency increased HSV-1 replication and host susceptibility to HSV-1 infection. Mechanistically, USP12 inhibited the proteasome-dependent degradation of IFI16 through its deubiquitinase activity, thereby maintaining IFI16 stability and promoting IFI16-STING-IRF3- and p65-mediated antiviral signaling. Overall, our findings demonstrate an essential role of USP12 in DNA-sensing signaling and contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.
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