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• W1946603676 abstract "Dynasore has been used extensively as an inhibitor of clathrin-mediated endocytosis. While studying the role of endocytosis in LPS-induced signalling events, we discovered that dynasore itself induced activation of NF-κB, independently of its effects on endocytosis and without involving the Toll-like receptor 4 signalling pathways. The purpose of this study was to characterize this novel effect and to explore the underlying mechanism of action.We utilized gel electrophoresis, microscopy, gene knockdown and luciferase-based promoter activity to evaluate the effect of dynasore on cell signalling pathways and to delineate the mechanisms involved in its effects,Dynasore activated the NF-κB and IFN-β pathways by activating mitochondrial antiviral signalling protein (MAVS). We showed that MAVS is activated by NOX/Rac and forms high molecular weight aggregates, similar to that observed in response to viral infection. We also demonstrated that dynasore-induced activation of JNK occurs downstream of MAVS and is required for activation of NF-κB and IFN-β.These findings demonstrate a novel effect of dynasore on cell signalling. We describe a novel Rac1-, ROS- and MAVS-mediated signalling cascade through which dynasore dramatically activates NF-κB, mimicking the viral induction of this key inflammatory signalling pathway. Our results call attention to the need for a broader interpretation of results when dynasore is used in its traditional fashion as an inhibitor of clathrin-mediated endocytosis. These results suggest the intriguing possibility that dynasore or one of its analogues might be of value as an antiviral therapeutic strategy or vaccine adjuvant." @default.
• W1946603676 created "2016-06-24" @default.
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• W1946603676 date "2015-05-15" @default.
• W1946603676 modified "2023-09-28" @default.
• W1946603676 title "Dynasore enhances the formation of mitochondrial antiviral signalling aggregates and endocytosis-independent NF-κB activation" @default.
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• W1946603676 doi "https://doi.org/10.1111/bph.13162" @default.
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