Zhao Xueyan, Yan Xiaolong, Huo Ruixuan, Xu Tianjun
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China; Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, 201306, China.
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China; Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education, 201306, China; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, 201306, China.
Dev Comp Immunol. 2020 May;106:103632. doi: 10.1016/j.dci.2020.103632. Epub 2020 Jan 24.
Tightly regulation of NF-κB signaling is essential to innate and adaptive immune responses, but its regulatory mechanism remains unclear in various organisms, especially teleost fish. In this study, we reported that IRF3 attenuates the inhibitory effect of IκBα on NF-κB activation in teleost fish. Overexpression of IRF3 can promote IκBα degradation, whereas its knockdown can relieve degradation of IκBα. IRF3 promoted the degradation of IκBα protein, but this effect could be inhibited by MG132 treatment. IRF3 is crucial for the polyubiquitination and proteasomal degradation of IκBα. Our findings indicate that IRF3 regulates NF-κB pathway by targeting IκBα for ubiquitination and degradation. This study provides novel evidence on the regulation of innate immune signaling pathways in teleost fish and thus provides new insights into the regulatory mechanisms in mammals.
对NF-κB信号通路的严格调控对于先天免疫和适应性免疫反应至关重要，但其调控机制在各种生物体中仍不清楚，尤其是硬骨鱼。在本研究中，我们报道了IRF3减弱了硬骨鱼中IκBα对NF-κB激活的抑制作用。IRF3的过表达可促进IκBα的降解，而其敲低则可缓解IκBα的降解。IRF3促进了IκBα蛋白的降解，但这种作用可被MG132处理抑制。IRF3对于IκBα的多聚泛素化和蛋白酶体降解至关重要。我们的研究结果表明，IRF3通过靶向IκBα进行泛素化和降解来调节NF-κB通路。本研究为硬骨鱼先天免疫信号通路的调控提供了新证据，从而为哺乳动物的调控机制提供了新见解。
