ArticleScience advances2016
PPM1A silences cytosolic RNA sensing and antiviral defense through direct dephosphorylation of MAVS and TBK1.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 70 citations in OpenAlex.
- Targeting WIP1 reprograms immunosuppressive tumor microenvironment to potentiate immunotherapy response in colorectal cancer.Cell death and differentiation · 2026Article
- Sarbecoviruses Suppress Innate Immunity by Recruiting PPM1A to Modulate STAT2 and ORF9b Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ALOX15 orchestrates mitochondrial antiviral immunity and serves as a host target for anti-influenza therapy.Nature immunology · 2026Article
- Review
- Glycolytic enzyme PGK1 restricts viral replication via a glycolysis-independent mechanism.Science China. Life sciences · 2026Article
- A Bifunctional T3SS-Effector Simultaneously Cleaves Host MAP Kinase and Inhibits PPM1A Phosphatase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Old dogs-new tricks: multifaceted functions of MAVS beyond antivirus activity in human health and diseases.Cell & bioscience · 2025Review
- Aggregatin is a mitochondrial regulator of MAVS activation to drive innate immunity.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Frk positively regulates innate antiviral immunity by phosphorylating TBK1.Frontiers in microbiology · 2025Article
- Exploring the role of mitochondrial antiviral signaling protein in cardiac diseases.Frontiers in immunology · 2025Review
- Protein phosphatase PP2Cα S-glutathionylation regulates cell migration.The Journal of biological chemistry · 2024Article
- TRIM28 facilitates type I interferon activation by targeting TBK1.Frontiers in immunology · 2024Article
- Protein phosphatase PPM1A inhibition attenuates osteoarthritis via regulating TGF-β/Smad2 signaling in chondrocytes.JCI insight · 2023Article
- Article
- Stress-Induced Immunosuppression Affects Immune Response to Newcastle Disease Virus Vaccine via Circulating miRNAs.Animals : an open access journal from MDPI · 2022Article
- The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation.Nature communications · 2022Article
- TRIM18 is a critical regulator of viral myocarditis and organ inflammation.Journal of biomedical science · 2022Article
- Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The role of TBK1 in cancer pathogenesis and anticancer immunity.Journal of experimental & clinical cancer research : CR · 2022Review
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytosolic RNA sensing is a prerequisite for initiation of innate immune response against RNA viral pathogens. Signaling through RIG-I (retinoic acid-inducible gene I)-like receptors (RLRs) to TBK1 (Tank-binding kinase 1)/IKKε (IκB kinase ε) kinases is transduced by mitochondria-associated MAVS (mitochondrial antiviral signaling protein). However, the precise mechanism of how MAVS-mediated TBK1/IKKε activation is strictly controlled still remains obscure. We reported that protein phosphatase magnesium-dependent 1A (PPM1A; also known as PP2Cα), depending on its catalytic ability, dampened the RLR-IRF3 (interferon regulatory factor 3) axis to silence cytosolic RNA sensing signaling. We demonstrated that PPM1A was an inherent partner of the TBK1/IKKε complex, targeted both MAVS and TBK1/IKKε for dephosphorylation, and thus disrupted MAVS-driven formation of signaling complex. Conversely, a high level of MAVS can dissociate the TBK1/PPM1A complex to override PPM1A-mediated inhibition. Loss of PPM1A through gene ablation in human embryonic kidney 293 cells and mouse primary macrophages enabled robustly enhanced antiviral responses. Consequently, Ppm1a(-/-) mice resisted to RNA virus attack, and transgenic zebrafish expressing PPM1A displayed profoundly increased RNA virus vulnerability. These findings identify PPM1A as the first known phosphatase of MAVS and elucidate the physiological function of PPM1A in antiviral immunity on whole animals.
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