دورية أكاديمية
FAT10 inhibits TRIM21 to down-regulate antiviral type-I interferon secretion.
| العنوان: | FAT10 inhibits TRIM21 to down-regulate antiviral type-I interferon secretion. |
|---|---|
| المؤلفون: | Saxena K; https://ror.org/0546hnb39 Department of Biology, Division of Immunology, University of Konstanz, Konstanz, Germany., Inholz K; https://ror.org/0546hnb39 Department of Biology, Division of Immunology, University of Konstanz, Konstanz, Germany., Basler M; https://ror.org/0546hnb39 Department of Biology, Division of Immunology, University of Konstanz, Konstanz, Germany.; https://ror.org/030dhdf69 Biotechnology Institute Thurgauhttps://ror.org/0546hnb39 at the University of Konstanz, Kreuzlingen, Switzerland., Aichem A; https://ror.org/0546hnb39 Department of Biology, Division of Immunology, University of Konstanz, Konstanz, Germany Annette.Aichem@bitg.ch.; https://ror.org/030dhdf69 Biotechnology Institute Thurgauhttps://ror.org/0546hnb39 at the University of Konstanz, Kreuzlingen, Switzerland. |
| المصدر: | Life science alliance [Life Sci Alliance] 2024 Jul 08; Vol. 7 (9). Date of Electronic Publication: 2024 Jul 08 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Life Science Alliance, LLC Country of Publication: United States NLM ID: 101728869 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2575-1077 (Electronic) Linking ISSN: 25751077 NLM ISO Abbreviation: Life Sci Alliance Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Woodbury, NY] : Life Science Alliance, LLC, [2018]- |
| مواضيع طبية MeSH: | Ribonucleoproteins*/metabolism , Ribonucleoproteins*/genetics , Interferon Type I*/metabolism , Ubiquitination* , Ubiquitins*/metabolism , Ubiquitins*/genetics , Proteasome Endopeptidase Complex*/metabolism, Humans ; Down-Regulation ; HEK293 Cells ; Signal Transduction ; Influenza A virus/physiology ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitin-Protein Ligases/genetics ; Proteolysis ; Animals |
| مستخلص: | The ubiquitin-like modifier FAT10 is upregulated under pro-inflammatory conditions, targets its substrates for proteasomal degradation and functions as a negative regulator of the type-I IFN response. Influenza A virus infection upregulates the production of type-I IFN and the expression of the E3 ligase TRIM21, which regulates type-I IFN production in a positive feedback manner. In this study, we show that FAT10 becomes covalently conjugated to TRIM21 and that this targets TRIM21 for proteasomal degradation. We further show that the coiled-coil and PRYSPRY domains of TRIM21 and the C-terminal diglycine motif of FAT10 are important for the TRIM21-FAT10 interaction. Moreover, upon influenza A virus infection and in the presence of FAT10 the total ubiquitination of TRIM21 is reduced and our data reveal that the FAT10-mediated degradation of TRIM21 diminishes IFNβ production. Overall, this study provides strong evidence that FAT10 down-regulates the antiviral type-I IFN production by modulating additional molecules of the RIG-I signaling pathway besides the already published OTUB1. In addition, we elucidate a novel mechanism of FAT10-mediated proteasomal degradation of TRIM21 that regulates its stability. (© 2024 Saxena et al.) |
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| المشرفين على المادة: | 0 (SS-A antigen) 0 (Ribonucleoproteins) 0 (Interferon Type I) 0 (Ubiquitins) 0 (UBD protein, human) EC 3.4.25.1 (Proteasome Endopeptidase Complex) EC 2.3.2.27 (Ubiquitin-Protein Ligases) |
| تواريخ الأحداث: | Date Created: 20240708 Date Completed: 20240708 Latest Revision: 20240711 |
| رمز التحديث: | 20240711 |
| مُعرف محوري في PubMed: | PMC11231494 |
| DOI: | 10.26508/lsa.202402786 |
| PMID: | 38977311 |
| قاعدة البيانات: | MEDLINE |
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