Abstract |
The transcription factor IRF3 is phosphorylated in response to viral infection, and it subsequently forms a homodimer and translocates into the nucleus to induce the transcription of genes important for antiviral immunity, such as type I interferons (IFNs). This multistep process is essential for host defense against viral infection, but its regulation remains elusive. Here, we report that the EF-hand protein calmodulin-like 6 (CALML6) directly bound to the phosphorylated serine-rich (SR) region of IRF3 and impaired its dimerization and nuclear translocation. Enforced CALML6 expression suppressed viral infection-induced production of IFN-β and expression of IFN-stimulated genes (ISGs), whereas CALML6 deficiency had the opposite effect. In addition, impaired IFN-β and ISG expression in bone-marrow-derived macrophages and tissues of CALML6 transgenic mice promoted viral replication. These findings identify a phosphorylation-dependent negative feedback loop that maintains the homeostasis of antiviral innate immunity.
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Authors | Ziyang Wang, Chunjie Sheng, Chen Yao, Hongyuan Chen, Dan Wang, Shuai Chen |
Journal | Cell reports
(Cell Rep)
Vol. 26
Issue 5
Pg. 1273-1285.e5
(01 29 2019)
ISSN: 2211-1247 [Electronic] United States |
PMID | 30699354
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Antiviral Agents
- CALML6 protein, human
- Calcium-Binding Proteins
- Interferon Regulatory Factor-3
- Interferon Type I
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Topics |
- Animals
- Antiviral Agents
(metabolism)
- Calcium-Binding Proteins
(chemistry, deficiency, metabolism)
- Cytoplasm
(metabolism)
- EF Hand Motifs
- HEK293 Cells
- Humans
- Immunity, Innate
- Interferon Regulatory Factor-3
(metabolism)
- Interferon Type I
(metabolism)
- Mice, Transgenic
- Phosphorylation
- Protein Binding
- Protein Domains
- Protein Multimerization
- Signal Transduction
- Virus Replication
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