ArticleCell & bioscience2018
RINCK-mediated monoubiquitination of cGAS promotes antiviral innate immune responses.
Article in Cell & bioscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 55 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Lactylation: a novel post-translational modification for cGAS-STING pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Biochemical Engineering Perspective on cGAS: From Enzyme Discovery to Potential Industrial Application.Chembiochem : a European journal of chemical biology · 2026Review
- Roles and Mechanisms of TRIM Family Proteins in Inflammation in the Brain and Beyond.International journal of molecular sciences · 2026Review
- HSV-2 genome recognition by nuclear cGAS instigates IFN-β production and influences inflammasome activation duringFrontiers in immunology · 2026Article
- Deubiquitinating enzyme JOSD2 modulates cGAS to facilitate immune evasion in colorectal cancer.Oncoimmunology · 2025Article
- Breaking barriers: The cGAS-STING pathway as a novel frontier in cancer immunotherapy.Cancer communications (London, England) · 2025Review
- cGAS, an innate dsDNA sensor with multifaceted functions.Cell insight · 2025Review
- cGAS-STING: mechanisms and therapeutic opportunities.Science China. Life sciences · 2025Review
- Identification and development of cGAS inhibitors and their uses to treat Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- cGAS-STING signaling: a therapeutic target in inflammatory bowel disease and related colorectal cancer.Frontiers in immunology · 2025Review
- The role of cGAS-STING pathway ubiquitination in innate immunity and multiple diseases.Frontiers in immunology · 2025Review
- Review
- The role of the cGAS-STING signaling pathway in viral infections, inflammatory and autoimmune diseases.Acta pharmacologica Sinica · 2024Review
- The RNA-binding proteins regulate innate antiviral immune signaling by modulating pattern recognition receptors.Virology journal · 2024Review
- Unraveling the cGAS/STING signaling mechanism: impact on glycerolipid metabolism and diseases.Frontiers in medicine · 2024Review
- Targeting the PRMT1-cGAS-STING signaling pathway to enhance the anti-tumor therapeutic efficacy.Journal of cancer biology · 2024Article
- Host Factors Modulate Virus-Induced IFN Production via Pattern Recognition Receptors.Journal of inflammation research · 2024Review
- Nuclear cGAS restricts L1 retrotransposition by promoting TRIM41-mediated ORF2p ubiquitination and degradation.Nature communications · 2023Article
- Significance of the cGAS-STING Pathway in Health and Disease.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAs an important danger signal, the presence of DNA in cytoplasm triggers potent immune responses. Cyclic GMP-AMP synthase (cGAS) is a recently characterized key sensor for cytoplasmic DNA. The engagement of cGAS with DNA leads to the synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which binds and activates the downstream adaptor protein STING to promote type I interferon production. Although cGAS has been shown to play a pivotal role in innate immunity, the exact regulation of cGAS activation is not fully understood.
resultsWe report that an E3 ubiquitin ligase, RING finger protein that interacts with C kinase (RINCK, also known as tripartite motif protein 41, TRIM41), is critical for cGAS activation by mediating the monoubiquitination of cGAS. Using CRISPR/Cas9, we generated RINCK-deletion cells and showed that the deficiency of RINCK resulted in dampened interferon production in response to cytosolic DNA. Consistently, the RINCK-deletion cells also exhibited insufficient interferon production upon herpes simplex virus 1, a DNA virus, infection. As a result, the viral load in RINCK-deficient cells was significantly higher than that in wild-type cells. We also found that RINCK deficiency inhibited the up-stream signaling of DNA-triggered interferon production pathway, which was reflected by the phosphorylation of the TANK-binding kinase 1 and the interferon regulatory factor 3. Interestingly, we found that RINCK binds to cGAS and promotes the monoubiquitination of cGAS, thereby positively regulating the cGAS-mediated cGAMP synthesis.
conclusionsOur study reveals that monoubiquitination is an important regulation for cGAS activation and uncovers a critical role of RINCK in the cGAS-mediated innate immunity.
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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.