Formation of SUMO3-conjugated chains of MAVS induced by poly(dA:dT), a ligand of RIG-I, enhances the aggregation of MAVS that drives the secretion of interferon-β in human keratinocytes
| Autor: | Go Woon Choi, Jung-Hoon Kang, Mihee Yun, Seong-Beom Lee, Yujin Lee |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Keratinocytes
0301 basic medicine Biophysics SUMO protein SUMO2 Ligands Biochemistry Cell Line Protein Aggregates 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Poly dA-dT Protein Domains Interferon RNA polymerase medicine Humans Secretion RNA Small Interfering Receptors Immunologic Ubiquitins Molecular Biology Adaptor Proteins Signal Transducing Sequence Deletion Chemistry RIG-I Sumoylation RNA Interferon-beta Cell Biology Ligand (biochemistry) Salicylates Cell biology 030104 developmental biology 030220 oncology & carcinogenesis Ubiquitin-Conjugating Enzymes DEAD Box Protein 58 medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 522:939-944 |
| ISSN: | 0006-291X |
| Popis: | The retinoic-acid inducible gene (RIG)-I is a cytoplasmic pattern recognition receptor that senses single-stranded (ss) or double-stranded (ds) RNA. RIG-I also senses AT-rich dsDNA, poly(dA:dT), through the action of an RNA polymerase III-transcribed RNA intermediate. Upon the binding of an RNA ligand, RIG-I binds to the mitochondrial antiviral-signaling protein (MAVS) and induces the formation of filamentous aggregates of MAVS, leading to the formation of a signaling complex that drives Type I interferon (IFN) responses. In the current study, we investigated the issue of whether the SUMOylation of MAVS induced by poly(dA:dT) affects the aggregation of MAVS in the RIG-I/MAVS pathway in human keratinocytes. Our results show that the poly(dA:dT)-induced secretion of IFN-β was dependent on RIG-I and MAVS. The inhibition of SUMOylation by Ginkgolic acid or Ubc9 siRNA was found to inhibit the poly(dA:dT)-induced secretion of IFN-β, suggesting that the SUMOylation is required for the poly(dA:dT)-activated RIG-I/MAVS pathway, which drives the secretion of IFN-β. In addition, treatment with poly(dA:dT) enhanced the formation of polymeric chains of small-ubiquitin like modifiers (SUMO)3, but not SUMO1 and SUMO2, on MAVS. Our results also show that the conjugation of SUMO3 to MAVS induced by poly (dA:dT) enhanced the aggregation of MAVS. These collective results show that the formation of SUMO3-conjugated chains of MAVS induced by poly (dA:dT), a ligand of RIG-I, enhances the aggregation of MAVS which, in turn, drives the secretion of IFN-β in human keratinocytes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect