ArticlemBio2020
PPP6C Negatively Regulates STING-Dependent Innate Immune Responses.
Article in mBio, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- The Significance of cGAS-STING Signaling in Response to Oncogenic Viruses.Cell biochemistry and function · 2026Review
- The Role and Therapeutic Potential of the STING Signaling Pathway in the Pathogenesis of Diabetic Nephropathy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The CD97-PPM1G axis dampens antiviral immunity by dephosphorylating IRF7 in type I interferon pathway.PLoS pathogens · 2026Article
- Emerging Mechanistic Roles of STING Signaling in Kidney Diseases.The American journal of pathology · 2026Review
- Nuclear Fraction Proteome Analyses During rAAV Production of AAV2-Plasmid-Transfected HEK-293 Cells.International journal of molecular sciences · 2025Article
- Article
- ORF48 is required for optimal lytic replication of Kaposi's sarcoma-associated herpesvirus.PLoS pathogens · 2024Article
- The protein phosphatase PP6 promotes RIPK1-dependent PANoptosis.BMC biology · 2024Article
- Mycobacterial CpsA activates type I IFN signaling in macrophages via cGAS-mediated pathway.iScience · 2024Article
- Review
- Unraveling the cGAS/STING signaling mechanism: impact on glycerolipid metabolism and diseases.Frontiers in medicine · 2024Review
- Zebrafish TMEM47 is an effective blocker of IFN production during RNA and DNA virus infection.Journal of virology · 2023Article
- The Many Ways to Deal with STING.International journal of molecular sciences · 2023Review
- STING trafficking as a new dimension of immune signaling.The Journal of experimental medicine · 2023Article
- Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases.Zoological research · 2023Review
- DDIT3 antagonizes innate immune response to promote bovine alphaherpesvirus 1 replication via the DDIT3-SQSTM1-STING pathway.Virulence · 2022Article
- Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors.Biomedicines · 2022Review
- Deficiency of PPP6C protects TNF-induced necroptosis through activation of TAK1.Cell death & disease · 2022Article
- Activation and Evasion of Innate Immunity by Gammaherpesviruses.Journal of molecular biology · 2022Review
- The regulation of KSHV lytic reactivation by viral and cellular factors.Current opinion in virology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Stimulator of interferon genes (STING) is an essential adaptor protein of the innate DNA-sensing signaling pathway, which recognizes genomic DNA from invading pathogens to establish antiviral responses in host cells. STING activity is tightly regulated by several posttranslational modifications, including phosphorylation. However, specifically how the phosphorylation status of STING is modulated by kinases and phosphatases remains to be fully elucidated. In this study, we identified protein phosphatase 6 catalytic subunit (PPP6C) as a binding partner of Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 48 (ORF48), which is a negative regulator of the cyclic GMP-AMP synthase (cGAS)-STING pathway. PPP6C depletion enhances double-stranded DNA (dsDNA)-induced and 5'ppp double-stranded RNA (dsRNA)-induced but not poly(I:C)-induced innate immune responses. PPP6C negatively regulates dsDNA-induced IRF3 activation but not NF-κB activation. Deficiency of PPP6C greatly inhibits the replication of herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) as well as the reactivation of KSHV, due to increased type I interferon production. We further demonstrated that PPP6C interacts with STING and that loss of PPP6C enhances STING phosphorylation. These data demonstrate the important role of PPP6C in regulating STING phosphorylation and activation, which provides an additional mechanism by which the host responds to viral infection.
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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.