ArticleProtein & cell2020
Dephosphorylation of cGAS by PPP6C impairs its substrate binding activity and innate antiviral response.
Article in Protein & cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- cGAS in nucleus: The link between immune response and DNA damage repair.Frontiers in immunology · 2022Pooled it
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Spotlight on cGAS-STING: role in disease pathogenesis and therapeutic potential.Molecular biomedicine · 2026Review
- AARS1 promotes diabetic kidney disease through rewiring Akt and NF-κB signaling to suppress autophagy and sustain inflammation.Cellular & molecular biology letters · 2026Article
- Physalin F Promotes AFG3L2-Mediated Degradation of VISA/MAVS to Suppress Innate Immune Response to RNA Virus.Pathogens (Basel, Switzerland) · 2026Article
- HSV-2 genome recognition by nuclear cGAS instigates IFN-β production and influences inflammasome activation duringFrontiers in immunology · 2026Article
- Nuclear Fraction Proteome Analyses During rAAV Production of AAV2-Plasmid-Transfected HEK-293 Cells.International journal of molecular sciences · 2025Article
- cGAS, an innate dsDNA sensor with multifaceted functions.Cell insight · 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
- Functional Role of Protein Phosphatase-6 (Current medicinal chemistry · 2025Review
- PLK2-mediated phosphorylation of SQSTM1 S349 promotes aggregation of polyubiquitinated proteins upon proteasomal dysfunction.Autophagy · 2024Article
- Androgen receptor-mediated pharmacogenomic expression quantitative trait loci: implications for breast cancer response to AR-targeting therapy.Breast cancer research : BCR · 2024Article
- The protein phosphatase PP6 promotes RIPK1-dependent PANoptosis.BMC biology · 2024Article
- Genetic Encoding of Phosphorylated Amino Acids into Proteins.Chemical reviews · 2024Review
- Molecular Role of Protein Phosphatases in Alzheimer's and Other Neurodegenerative Diseases.Biomedicines · 2024Review
- Review
- 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
- PD-1 signaling negatively regulates the common cytokine receptor γ chain via MARCH5-mediated ubiquitination and degradation to suppress anti-tumor immunity.Cell research · 2023Article
- Mitochondrial DNA-triggered innate immune response: mechanisms and diseases.Cellular & molecular immunology · 2023Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cyclic GMP-AMP (cGAMP) synthase (cGAS) plays a critical role in host defense by sensing cytosolic DNA derived from microbial pathogens or mis-located cellular DNA. Upon DNA binding, cGAS utilizes GTP and ATP as substrates to synthesize cGAMP, leading to MITA-mediated innate immune response. In this study, we identified the phosphatase PPP6C as a negative regulator of cGAS-mediated innate immune response. PPP6C is constitutively associated with cGAS in un-stimulated cells. DNA virus infection causes rapid disassociation of PPP6C from cGAS, resulting in phosphorylation of human cGAS S435 or mouse cGAS S420 in its catalytic pocket. Mutation of this serine residue of cGAS impairs its ability to synthesize cGAMP upon DNA virus infection. In vitro experiments indicate that S420-phosphorylated mcGAS has higher affinity to GTP and enzymatic activity. PPP6C-deficiency promotes innate immune response to DNA virus in various cells. Our findings suggest that PPP6C-mediated dephosphorylation of a catalytic pocket serine residue of cGAS impairs its substrate binding activity and innate immune response, which provides a mechanism for keeping the DNA sensor cGAS inactive in the absence of infection to avoid autoimmune response.
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Registered trials
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