ArticleProceedings of the National Academy of Sciences of the United States of America2019
PTPN1/2-mediated dephosphorylation of MITA/STING promotes its 20S proteasomal degradation and attenuates innate antiviral response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 78 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- PTPN2 inhibition unleashes response to STING agonism in head and neck squamous cell cancer.Nature communications · 2026Article
- Roles of the cGAS-STING signaling pathway in viral latency.Journal of virology · 2026Review
- Phosphorylation of FBXL3 mediates GLDC polyubiquitination to suppress MHC-I expression and promote cancer immune evasion.Cell insight · 2026Article
- Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- A Novel Tyrosine Kinase Axis in Innate Immune Signaling.Viruses · 2025Review
- Unveiling EXOC4/SEC8: a key player in enhancing antiviral immunity by inhibiting the FBXL19-STING1-SQSTM1 signaling axis.Autophagy · 2025Article
- SARS-CoV-2-induced damage to rat cortical neuronal networks ex vivo is mediated by the pro-inflammatory activation of the cGAS-STING pathway.Journal of neurovirology · 2025Article
- ZDHHC11-mediated palmitoylation alleviates chondrocyte senescence and serves as a therapeutic target for osteoarthritis.Nature aging · 2025Article
- Beyond interferons: Non-canonical roles of MITA/STING.Cell insight · 2025Review
- IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner.Cell insight · 2025Article
- The cGAS-STING axis: a comprehensive review from immune defense to disease pathogenesis.Immunologic research · 2025Review
- Regulation of cGAS-STING signalling and its diversity of cellular outcomes.Nature reviews. Immunology · 2025Review
- The conserved poxvirus membrane entry-fusion apparatus component OPG147 targets MITA/STING for immune evasion.PLoS pathogens · 2025Article
- Autoinflammatory encephalopathy due to PTPN1 haploinsufficiency: a case series.The Lancet. Neurology · 2025Article
- The monkeypox virus-host interplays.Cell insight · 2024Review
- The role of the cGAS-STING signaling pathway in viral infections, inflammatory and autoimmune diseases.Acta pharmacologica Sinica · 2024Review
- Ursonic acid from medicinal herbs inhibits PRRSV replication through activation of the innate immune response by targeting the phosphatase PTPN1.Veterinary research · 2024Article
- STING guides the STX17-SNAP29-VAMP8 complex assembly to control autophagy.Cell insight · 2024Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon cytosolic viral DNA stimulation, cGMP-AMP synthase (cGAS) catalyzes synthesis of 2'3'cGMP-AMP (cGAMP), which binds to the adaptor protein MITA (mediator of IRF3 activation, also called STING, stimulator of IFN genes) and induces innate antiviral response. How the activity of MITA/STING is regulated to avoid excessive innate immune response is not fully understood. Here we identified the tyrosine-protein phosphatase nonreceptor type (PTPN) 1 and 2 as MITA/STING-associated proteins. PTPN1 and PTPN2 are associated with MITA/STING following viral infection and dephosphorylate MITA/STING at Y245. Dephosphorylation of MITA/STING leads to its degradation via the ubiquitin-independent 20S proteasomal pathway, which is dependent on the intrinsically disordered region (IDR) of MITA/STING. Deficiencies of PTPN1 and PTPN2 enhance viral DNA-induced transcription of downstream antiviral genes and innate antiviral response. Our findings reveal that PTPN1/2-mediated dephosphorylation of MITA/STING and its degradation by the 20S proteasomal pathway is an important regulatory mechanism of innate immune response to DNA virus.
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