ArticleNucleic acids research2022
USP15 promotes cGAS activation through deubiquitylation and liquid condensation.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- β-carboline derivative Z86 alleviates pulmonary fibrosis via suppressing TGF-β/Smad signaling.Natural products and bioprospecting · 2026Article
- Structural insights into ubiquitin recognition by USP15 revealed through a covalent activity-based probe.Communications biology · 2026Article
- Biochemical Engineering Perspective on cGAS: From Enzyme Discovery to Potential Industrial Application.Chembiochem : a European journal of chemical biology · 2026Review
- The cGAS-STING pathway at the crossroads of neuroimmunology: bridging innate immunity to aging and neurodegeneration.Biomarker research · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- IL27RA promotes the proliferation and metastasis of hepatocellular carcinoma cells by regulating TGFβR1.Scientific reports · 2025Article
- De novo design of protein condensation inhibitors by targeting an allosteric site of cGAS.Nature communications · 2025Article
- Phase Separation: Orchestrating Biological Adaptations to Environmental Fluctuations.International journal of molecular sciences · 2025Review
- Protein Drug Targets for Abdominal Aortic Aneurysm and Proteomic Associations Between Modifiable Risk Factors and Abdominal Aortic Aneurysm.Journal of the American Heart Association · 2025Article
- Emerging regulatory mechanisms and functions of biomolecular condensates: implications for therapeutic targets.Signal transduction and targeted therapy · 2025Review
- NASP Promotes Triple-negative Breast Cancer Progression and Metastasis by Stabilizing YAP in a USP15-Dependent Way.International journal of biological sciences · 2025Article
- Liquid-liquid phase separation: an emerging perspective on the tumorigenesis, progression, and treatment of tumors.Frontiers in immunology · 2025Review
- The role of cGAS-STING pathway ubiquitination in innate immunity and multiple diseases.Frontiers in immunology · 2025Review
- Liquid-liquid phase separation in innate immunity.Trends in immunology · 2024Review
- ADP-Hep-Induced Liquid Phase Condensation of TIFA-TRAF6 Activates ALPK1/TIFA-Dependent Innate Immune Responses.Research (Washington, D.C.) · 2024Article
- Phase separation in cGAS-STING signaling.Frontiers of medicine · 2023Review
- Phase Separation: The Robust Modulator of Innate Antiviral Signaling and SARS-CoV-2 Infection.Pathogens (Basel, Switzerland) · 2023Review
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
Double-stranded DNA (dsDNA) is recognized as a danger signal by cyclic GMP-AMP synthase (cGAS), which triggers innate immune responses. cGAS activity must be properly regulated to maintain immune homeostasis. However, the mechanism by which cGAS activation is controlled remains to be better understood. In this study, we identified USP15 as a cGAS-interacting partner. USP15 promoted DNA-induced cGAS activation and downstream innate immune responses through a positive feedback mechanism. Specifically, USP15 deubiquitylated cGAS and promoted its activation. In the absence of DNA, USP15 drove cGAS dimerization and liquid condensation through the USP15 intrinsic disordered region (IDR), which prepared cGAS for a rapid response to DNA. Upon DNA stimulation, USP15 was induced to express and boost cGAS activation, functioning as an efficient amplifier in innate immune signal transduction. In summary, the positive role played by USP15-mediated cGAS activation may be a novel regulatory mechanism in the fine-tuning of innate immunity.
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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.