TANK-binding kinase 1 (TBK1) is of central importance for the induction of type-I interferon (IFN) in response to pathogens. We identified the DEAD-box helicase DDX3X as an interaction partner of TBK1. TBK1 and DDX3X acted synergistically in their ability to stimulate the IFN promoter, whereas RNAi-mediated reduction of DDX3X expression led to an impairment of IFN production. Chromatin immunoprecipitation indicated that DDX3X is recruited to the IFN promoter upon infection with Listeria monocytogenes, suggesting a transcriptional mechanism of action. DDX3X was found to be a TBK1 substrate in vitro and in vivo. Phosphorylation-deficient mutants of DDX3X failed to synergize with TBK1 in their ability to stimulate the IFN promoter. Overall, our data imply that DDX3X is a critical effector of TBK1 that is necessary for type I IFN induction.
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http://dx.doi.org/10.1038/emboj.2008.126 | DOI Listing |
iScience
January 2025
Department of Oncology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003 Henan, China.
Esophageal carcinoma (EC) is one of the most common malignant tumors in the world. ECRG4 has been recently discovered to be downregulated in EC. However, the mechanism leading to reduced expression of ECRG4 in esophageal cancer remains obscure.
View Article and Find Full Text PDFFish Shellfish Immunol
January 2025
College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, 511464, China. Electronic address:
Nuclear factor-κB (NF-κB)/p65, a vital signaling molecule in the NF-κB pathway, participates in diverse physiological functions and host-virus interactions. However, the involvement of NF-κB/p65 in fish virus infection remains poorly understood. In this study, we explored the role of the p65 in virus infection and its impact on IL-18 regulation in largemouth bass (Micropterus salmoides).
View Article and Find Full Text PDFVet Microbiol
January 2025
Key Laboratory of Livestock and Poultry Multi-omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, Shandong, China. Electronic address:
Porcine reproductive and respiratory syndrome virus (PRRSV) has become one of the most economically important diseases to the global pig industry. RNase L is a ubiquitous cellular endoribonuclease that is activated upon the binding of a specific ligand, 2',5'-linked oligoadenylates (2-5 A), which is synthesized by oligoadenylate synthetases (OASs). However, whether Sus scrofa RNase L (sRNase L) could inhibit PRRSV replication and its mechanism have not been fully elucidated.
View Article and Find Full Text PDFJ Biol Chem
January 2025
State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China. Electronic address:
Melanoma differentiation-associated gene 5 (MDA5) initiates type I interferon (IFN) production by detecting cytosolic viral RNA. Mammalian MDA5 is an IFN-inducible gene and controlled by IFN regulatory factor 1 (IRF1). Teleost MDA5 also induces type I IFN production in response to viruses, yet its regulation remains largely unexplored.
View Article and Find Full Text PDFJ Virol
January 2025
Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China.
Unlabelled: Although fish possess an effective interferon (IFN) system to defend against viral infection, grass carp reovirus (GCRV) still causes epidemic hemorrhagic disease and tremendous economic loss in grass carp. Therefore, it is necessary to investigate the immune escape strategies employed by GCRV. In this study, we show that the structural protein VP4 of GCRV (encoded by the S6 segment) significantly restricts IFN expression by degrading stimulator of IFN genes (STING) through the autophagy-lysosome-dependent pathway.
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