ArticlePLoS pathogens2016
Deubiquitinase USP2a Sustains Interferons Antiviral Activity by Restricting Ubiquitination of Activated STAT1 in the Nucleus.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Identification of the E3 ligase TRIM21 as a crucial regulator of STAT1 in metabolic dysfunction-associated steatohepatitis.Cell communication and signaling : CCS · 2026Article
- GDP-bound Rab37 modulates M2-like tumor-associated macrophage polarization by attenuating STAT1 translocation to downregulate the type I IFN pathway.British journal of cancer · 2025Article
- Inhibiting the Otub1/phosphorylated STAT3 axis for the treatment of non-small cell lung cancer.Acta pharmacologica Sinica · 2025Article
- Roles of deubiquitinases in urologic cancers (Review).Oncology letters · 2024Review
- Ceftazidime is a potential drug to inhibit cell proliferation by increasing cellular p27.The Journal of antibiotics · 2024Article
- Dampening of ISGylation of RIG-I by ADAP regulates type I interferon response of macrophages to RNA virus infection.PLoS pathogens · 2024Article
- Article
- USP2 promotes tumor immune evasion via deubiquitination and stabilization of PD-L1.Cell death and differentiation · 2023Article
- TRAF3/STAT6 axis regulates macrophage polarization and tumor progression.Cell death and differentiation · 2023Article
- Human cytomegalovirus UL138 interaction with USP1 activates STAT1 in infection.PLoS pathogens · 2023Article
- Human Cytomegalovirus UL138 Interaction with USP1 Activates STAT1 in infection.bioRxiv : the preprint server for biology · 2023Article
- LATS1 is a central signal transmitter for achieving full type-I interferon activity.Science advances · 2022Article
- The Role of Deubiquitinases in Virus Replication and Host Innate Immune Response.Frontiers in microbiology · 2022Review
- Ubiquitin E3 ligase MID1 inhibits the innate immune response by ubiquitinating IRF3.Immunology · 2021Article
- Suppression of USP7 induces BCR-ABL degradation and chronic myelogenous leukemia cell apoptosis.Cell death & disease · 2021Article
- Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination.Viruses · 2021Review
- Bmp8a is an essential positive regulator of antiviral immunity in zebrafish.Communications biology · 2021Article
- USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes.International journal of molecular sciences · 2021Review
- An Integrated View of Deubiquitinating Enzymes Involved in Type I Interferon Signaling, Host Defense and Antiviral Activities.Frontiers in immunology · 2021Review
- Small-molecule inhibitors of ubiquitin-specific protease 7 enhance type-I interferon antiviral efficacy by destabilizing SOCS1.Immunology · 2020Article
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
STAT1 is a critical transcription factor for regulating host antiviral defenses. STAT1 activation is largely dependent on phosphorylation at tyrosine 701 site of STAT1 (pY701-STAT1). Understanding how pY701-STAT1 is regulated by intracellular signaling remains a major challenge. Here we find that pY701-STAT1 is the major form of ubiquitinated-STAT1 induced by interferons (IFNs). While total STAT1 remains relatively stable during the early stages of IFNs signaling, pY701-STAT1 can be rapidly downregulated by the ubiquitin-proteasome system. Moreover, ubiquitinated pY701-STAT1 is located predominantly in the nucleus, and inhibiting nuclear import of pY701-STAT1 significantly blocks ubiquitination and downregulation of pY701-STAT1. Furthermore, we reveal that the deubiquitinase USP2a translocates into the nucleus and binds to pY701-STAT1, and inhibits K48-linked ubiquitination and degradation of pY701-STAT1. Importantly, USP2a sustains IFNs-induced pY701-STAT1 levels, and enhances all three classes of IFNs- mediated signaling and antiviral activity. To our knowledge, this is the first identified deubiquitinase that targets activated pY701-STAT1. These findings uncover a positive mechanism by which IFNs execute efficient antiviral signaling and function, and may provide potential targets for improving IFNs-based antiviral therapy.
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