ArticleSignal transduction and targeted therapy2024
AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation.
Article in Signal transduction and targeted therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Early Life Exposure to Air Pollutants and Childhood Asthma.Current allergy and asthma reports · 2026Review
- Update on environmental determinants of allergic diseases.The Journal of allergy and clinical immunology · 2026Review
- Replication-competent SIVcpz CRISPR screen identifies barriers to successful cross-species transmission.Journal of virology · 2026Article
- Dose-resolved control of somatic reprogramming by Rora.Stem cell reports · 2026Article
- Large-Scaled Proteomics Analysis for Glaucoma: Integrated Genetics, Multi-Omics, UK Biobank and Therapeutic Analysis.Investigative ophthalmology & visual science · 2026Article
- TRIM59 promotes immune evasion and tumor progression in lung adenocarcinoma via ubiquitin- proteasomal degradation of IRF3.Frontiers in immunology · 2026Article
- The deubiquitinase USP35: from an oncogenic hub to a therapeutic target in human cancers.Frontiers in oncology · 2026Review
- Targeting TRIM15-mediated Axin1 depolymerization suppresses Wnt signaling and inhibits colorectal cancer growth.Cell death & disease · 2025Article
- Prognostic Significance of HMGA1 in Hepatocellular Carcinoma: Implications for Tumor Progression and Targeted Therapy.Archives of Iranian medicine · 2025Article
- A Unique Trimeric Assembly of Human Dishevelled 1 PDZ Domain in Crystal: Implication of Homo- and Hetero-Oligomerization During Wnt Signaling Process.Molecules (Basel, Switzerland) · 2025Article
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- The role of cellular heterogeneity in thyroid cancer: a multi-modal analysis approach with Mendelian randomization.Discover oncology · 2025Article
- PLAGL2 as a prognostic biomarker and an EMT-promoting factor in PDAC.Scientific reports · 2025Article
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Authors and funding
30 authors.
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Abstract
Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.
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