DYRK2 Negatively Regulates Type I Interferon Induction by Promoting TBK1 Degradation via Ser527 Phosphorylation

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In recent years, the mechanisms of innate antiviral immune responses mediated by pattern recognition receptors (PRRs) have been heavily investigated. All PRRs require the key molecule TANK-binding kinase 1 (TBK1) to activate the transcription factor IRF3, which leads to type I interferon induction and the cellular antiviral response. Here, we identified the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (DYRK2) as a negative regulator of TBK1. DYRK2 inhibited the virus-triggered induction of type I interferon and promoted K48-linked ubiquitination and the degradation of TBK1 in a manner that depended on its kinase activity. We further found that DYRK2 phosphorylated Ser527 of TBK1, which is essential for the recruitment of NLRP4 and for the E3 ubiquitin ligase DTX4 to degrade TBK1. Our findings suggest that DYRK2 plays an important role in innate immune responses to viruses by modulating TBK1 activity and provide important insights into the intricate regulatory mechanisms of the innate immune response against viruses.

Vyšlo v časopise: DYRK2 Negatively Regulates Type I Interferon Induction by Promoting TBK1 Degradation via Ser527 Phosphorylation. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005179
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005179

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