BinCARD2 as a positive regulator of interferon response in innate immunity
| Autor: | Takeshi Kameyama, Akinori Takaoka, Hiraku Suzuki |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
BinCARD Biophysics Apoptosis Biology Biochemistry Vesicular stomatitis Indiana virus Cell Line 03 medical and health sciences 0302 clinical medicine Interferon medicine Gene silencing Humans Molecular Biology Adaptor Proteins Signal Transducing Gene knockdown Innate immune system Signal transducing adaptor protein Cell Biology Interferon-beta Immunity Innate Cell biology CARD Signaling Adaptor Proteins 030104 developmental biology TRIF 030220 oncology & carcinogenesis Mitochondrial Membranes CARD domain Vesicular Stomatitis medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 511(2) |
| ISSN: | 1090-2104 |
| Popis: | Innate immunity is a system that recognizes primarily and excludes pathogenic microorganism. MAVS/IPS-1/Cardif/Visa functions as an adapter protein for RIG-I like receptors (RLRs) and plays a key role in the production of antiviral proteins, interferons (IFNs), for RNA viruses. However, the activation mechanism is not fully understood. Here, we show that BinCARD isoform2 (BinCARD2), carrying CARD domain structure like MAVS, functions in innate immune response. Knockdown of BinCARD2 reduced the RLR ligand-induced expression of IFN-β mRNA and activation of the IFNB promoter. The activation of the IFNB promoter by overexpression of MAVS or TBK1 was suppressed by silencing of BinCARD2, but no effect on IFNB promoter activation by overexpression of TRIF or constitutive activated IRF-3. Furthermore, we confirmed that BinCARD2 protein associated with MAVS but not TBK1 by immunoprecipitation and colocalized with MAVS. Accordingly, we investigated whether BinCARD2 was involved in MAVS activation and showed that siBinCARD2 did not affect RIG-I/MAVS binding but impaired the MAVS oligomerization. Moreover, we infected A549 cells with vesicular stomatitis virus (VSV) and found that induction of IFN-β and IL-6 mRNA after VSV infection was decreased by BinCARD2 knockdown. Thus, these data may suggest that BinCARD2 associates with MAVS to positively modulate the oligomerization in the RIG-I like receptors pathway and activates innate immune response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect