ArticlePLoS pathogens2019
USP49 negatively regulates cellular antiviral responses via deconjugating K63-linked ubiquitination of MITA.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
- The RAB32-USP13 axis facilitates TOM40 mitochondrial localization to promote non-small cell lung cancer progression.Cell death and differentiation · 2026Article
- Ubiquitin-Specific Protease 49 Interacts with Bax to Modulate Apoptosis.International journal of molecular sciences · 2026Article
- DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2025Review
- HnRNPC triggers the degradation of MITA to suppress the interferon-mediated antiviral response.Veterinary research · 2025Article
- FBXO2 promotes hepatocellular carcinoma progression and sorafenib resistance by targeting USP49 for proteasomal degradation.Frontiers in immunology · 2025Article
- Type VII secretion system extracellular protein B targets STING to evade host anti-Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- MARCH5 promotes STING pathway activation by suppressing polymer formation of oxidized STING.EMBO reports · 2023Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- The Many Ways to Deal with STING.International journal of molecular sciences · 2023Review
- Unlocking STING as a Therapeutic Antiviral Strategy.International journal of molecular sciences · 2023Review
- USP49 deubiquitinase regulates the mitotic spindle checkpoint and prevents aneuploidy.Cell death & disease · 2023Article
- Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases.Zoological research · 2023Review
- SHP-1 knockdown suppresses mitochondrial biogenesis and aggravates mitochondria-dependent apoptosis induced by all trans retinal through the STING/AMPK pathways.Molecular medicine (Cambridge, Mass.) · 2022Article
- Genome-wide screening for deubiquitinase subfamily identifies ubiquitin-specific protease 49 as a novel regulator of odontogenesis.Cell death and differentiation · 2022Article
- The Role of REC8 in the Innate Immune Response to Viral Infection.Journal of virology · 2022Article
- Fbxo45 facilitates pancreatic carcinoma progression by targeting USP49 for ubiquitination and degradation.Cell death & disease · 2022Article
- K63 ubiquitination in immune signaling.Trends in immunology · 2022Review
- Oncogenic Activity of Glucocorticoid Receptor β Is Controlled by Ubiquitination-Dependent Interaction with USP49 in Glioblastoma Cells.Molecular cancer research : MCR · 2022Article
- The Role of Deubiquitinases in Virus Replication and Host Innate Immune Response.Frontiers in microbiology · 2022Review
- Regulation of cGAS/STING signaling and corresponding immune escape strategies of viruses.Frontiers in cellular and infection microbiology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mediator of IRF3 activation (MITA, also known as STING and ERIS) is an essential adaptor protein for cytoplasmic DNA-triggered signaling and involved in innate immune responses, autoimmunity and tumorigenesis. The activity of MITA is critically regulated by ubiquitination and deubiquitination. Here, we report that USP49 interacts with and deubiquitinates MITA after HSV-1 infection, thereby turning down cellular antiviral responses. Knockdown or knockout of USP49 potentiated HSV-1-, cytoplasmic DNA- or cGAMP-induced production of type I interferons (IFNs) and proinflammatory cytokines and impairs HSV-1 replication. Consistently, Usp49-/- mice exhibit resistance to lethal HSV-1 infection and attenuated HSV-1 replication compared to Usp49+/+ mice. Mechanistically, USP49 removes K63-linked ubiquitin chains from MITA after HSV-1 infection which inhibits the aggregation of MITA and the subsequent recruitment of TBK1 to the signaling complex. These findings suggest a critical role of USP49 in terminating innate antiviral responses and provide insights into the complex regulatory mechanisms of MITA activation.
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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.