Cao Baolan, Chen Ya, Cui Junxia, Sun Yuena, Xu Tianjun
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education, China; National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, China.
Dev Comp Immunol. 2022 Jul;132:104401. doi: 10.1016/j.dci.2022.104401. Epub 2022 Mar 23.
MyD88 is a typical street protein of the TLRs signaling pathway and is a central player in innate immune signaling, which can regulate the NF-κB signaling pathway and promote downstream inflammatory factors. However, studies on the molecular mechanisms of the MyD88-mediated NF-κB signaling pathway in teleosts have been poorly reported. In this study, we report that Zw10 targets MyD88 to inhibit NF-κB activation. Zw10 inhibits cell proliferation and MyD88-mediated innate immunity in fish. Zw10 interacts with MyD88, and its Δ2 domain is very critical for MyD88 degradation. In addition, we found that Zw10 degrade MyD88 by autophagy, thereby negatively regulating the MyD88-mediated NF-κB signaling pathway. This study not only enriches the research on the innate immunity of teleost fish, but also provides insights for the regulating mechanism for mammals.
髓样分化因子88（MyD88）是Toll样受体（TLR）信号通路的典型接头蛋白，是天然免疫信号传导的核心参与者，可调节核因子κB（NF-κB）信号通路并促进下游炎症因子的产生。然而，关于硬骨鱼中MyD88介导的NF-κB信号通路分子机制的研究报道较少。在本研究中，我们报道了ZW10蛋白靶向MyD88以抑制NF-κB激活。ZW10抑制鱼类细胞增殖和MyD88介导的天然免疫。ZW10与MyD88相互作用，其Δ2结构域对MyD88的降解非常关键。此外，我们发现ZW10通过自噬降解MyD88，从而负向调节MyD88介导的NF-κB信号通路。本研究不仅丰富了硬骨鱼天然免疫的研究，也为哺乳动物的调节机制提供了思路。
