ArticleNucleic acids research2021
Cooperative DNA binding mediated by KicGAS/ORF52 oligomerization allows inhibition of DNA-induced phase separation and activation of cGAS.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- DNA-triggered AIM2 condensation orchestrates immune activation and regulation.Protein & cell · 2026Article
- Roles of the cGAS-STING signaling pathway in viral latency.Journal of virology · 2026Review
- Liquid-liquid phase separation in the viral replication cycle: new paradigms and therapeutic opportunities.Archives of virology · 2026Review
- Alpha-herpesvirus US1 interacts with cGAS to suppress type I IFN responses and antiviral defense.PLoS pathogens · 2025Article
- Extracellular vesicles derived EBV tegument protein BRRF2 suppresses cGAS phase separation to promote anti-viral innate immune evasion.Nature communications · 2025Article
- The tegument protein VP22 of pseudorabies virus inhibits cGAS condensation by inducing nuclear-to-cytoplasmic translocation of DDX21.PLoS pathogens · 2025Article
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- WDR3 undergoes phase separation to mediate the therapeutic mechanism of Nilotinib against osteosarcoma.Journal of experimental & clinical cancer research : CR · 2025Article
- De novo design of protein condensation inhibitors by targeting an allosteric site of cGAS.Nature communications · 2025Article
- Circovirus Rep evades immune restriction by disrupting cGAS oligomerization and phase separation.PLoS pathogens · 2025Article
- Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025Review
- Rational design of chemical- and light-inducible cGAS activation based on mechanistic insights.Communications biology · 2025Article
- Emerging regulatory mechanisms and functions of biomolecular condensates: implications for therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Induction of translation-suppressive G3BP1hLife · 2025Article
- Prion-like domain mediated phase separation of ARID1A promotes oncogenic potential of Ewing's sarcoma.Nature communications · 2024Article
- Mycobacteriophage Alexphander GeneInternational journal of molecular sciences · 2024Article
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Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor that detects aberrant cytosolic DNA arising from pathogen invasions or genotoxic stresses. Upon binding to DNA, cGAS is activated and catalyzes the synthesis of cyclic GMP-AMP (cGAMP), which induces potent antimicrobial and antitumor responses. Kaposi sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that causes Kaposi sarcoma and several other malignancies. We previously reported that KSHV inhibitor of cGAS (KicGAS) encoded by ORF52, inhibits cGAS enzymatic activity, but the underlying mechanisms remained unclear. To define the inhibitory mechanisms, here we performed in-depth biochemical and functional characterizations of KicGAS, and mapped its functional domains. We found KicGAS self-oligomerizes and binds to double stranded DNA cooperatively. This self-oligomerization is essential for its DNA binding and cGAS inhibition. Interestingly, KicGAS forms liquid droplets upon binding to DNA, which requires collective multivalent interactions with DNA mediated by both structured and disordered domains coordinated through the self-oligomerization of KicGAS. We also observed that KicGAS inhibits the DNA-induced phase separation and activation of cGAS. Our findings reveal a novel mechanism by which DNA viruses target the host protein phase separation for suppression of the host sensing of viral nucleic acids.
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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.