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| Autori principali: | , , , , , , , , |
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| Natura: | Artículo científico |
| Lingua: | en |
| Pubblicazione: |
Proceedings of the National Academy of Sciences of the United States of America
2025
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| Soggetti: | |
| Accesso online: | https://pubmed.ncbi.nlm.nih.gov/39813248/ |
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Sommario:
- Direct lysine dimethylation of IRF3 by the methyltransferase SMYD3 attenuates antiviral innate immunity. Wang, Zixuan Chen, Xiaoyun Zhu, Chunchun Fan, Sijia Tang, Jinhua Deng, Hongyan Sun, Xueyi Liu, Xing Xiao, Wuhan Animals Immunity, Innate Histone-Lysine N-Methyltransferase Interferon Regulatory Factor-3 Zebrafish Mice Methylation Humans Lysine HEK293 Cells Phosphorylation Mice, Knockout Signal Transduction Interferon Type I Interferon regulatory factor 3 (IRF3) is the key transcription factor in the type I IFN signaling pathway, whose activation is regulated by multiple posttranslational modifications. Here, we identify SMYD3, a lysine methyltransferase, as a negative regulator of IRF3. SMYD3 interacts with IRF3 and catalyzes the dimethylation of IRF3 at lysine 39. This modification reduces IRF3 phosphorylation, dimerization, and subsequent nuclear translocation, leading to the inhibition of downstream type I interferon production. In addition, -deficient mice are more resistant to RNA and DNA viral infections. Zebrafish lacking or treated with the inhibitor BCI121 are also more resistant to viral infection. Our findings reveal a role for in the regulation of antiviral innate immunity and provide insight into a specific modulation of IRF3 that affects its activation.