PPM1A Regulates Antiviral Signaling by Antagonizing TBK1-Mediated STING Phosphorylation and Aggregation

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Innate antiviral immunity is essential for the host defense system that rapidly detects and eliminates invading viruses. STING, an endoplasmic reticulum (ER)-associated protein, plays important roles in the activation of type I IFN in response to DNA virus infection. Whereas excessive activation of STING can potentially cause lethal inflammatory diseases, STING activity must thus be precisely controlled to ensure the proper antiviral signaling transduction. However, the mechanisms of how STING activation is regulated are not fully understood. In this study, we find that PPM1A physically interacts with STING and negatively regulates STING-mediated antiviral signaling. Mechanistically, we find that PPM1A functions as a phosphatase that targets both STING and TBK1 for their dephosphorylation. Moreover, our study demonstrates that while TBK1 enhances STING aggregation in a kinase activity-dependent manner, PPM1A suppresses STING aggregation by dephosphorylating both STING and TBK1. Collectively, our study not only reveals that STING and TBK1 reciprocally regulate each other’s activity to elicit antiviral signaling, but also shows that PPM1A antagonizes STING aggregation by targeting both STING and TBK1, thereby maintaining proper antiviral responses.

Vyšlo v časopise: PPM1A Regulates Antiviral Signaling by Antagonizing TBK1-Mediated STING Phosphorylation and Aggregation. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004783
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004783

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