The von Hippel-Lindau tumor suppressor protein(VHL),an E3 ubiquitin ligase,functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors.Recent evidence suggests that mammalia...The von Hippel-Lindau tumor suppressor protein(VHL),an E3 ubiquitin ligase,functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors.Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway,although the specific molecular mechanisms remain unclear.Herein,the roles of mandarin fish(Siniperca chuatsi)VHL(scVHL)in the NF-κB signaling pathway and mandarin fish ranavirus(MRV)replication were explored.The transcription of scVHL was induced by immune stimulation and MRV infection,indicating a potential role in innate immunity.Dual-luciferase reporter gene assays and reverse transcription quantitative PCR(RT-qPCR)results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway.Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα,scIKKβ,scIκBα,or scp65.Co-immunoprecipitation(Co-IP)analysis identified scIκBαas a novel target protein of scVHL.Moreover,scVHL targeted scIκBαto catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway.Following MRV infection,NF-κB signaling remained activated,which,in turn,promoted MRV replication.These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication.This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.展开更多
基金supported by the National Key Research and Development Program of China(2022YFE0203900)Guangdong Key Research and Development Program(2021B0202040002 and 2022B1111030001)+4 种基金China Agriculture Research System(CARS-46)Guangdong Basic and Applied Basic Research Foundation(2021A1515010647)Basic and Applied Basic Research Project of Guangzhou Science and Technology Plan Project(202102020299)Science and Technology Planning Project of Guangdong(2023B1212060023)Guangdong Laboratory for Lingnan Modern Agriculture(NZ2021018)。
文摘The von Hippel-Lindau tumor suppressor protein(VHL),an E3 ubiquitin ligase,functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors.Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway,although the specific molecular mechanisms remain unclear.Herein,the roles of mandarin fish(Siniperca chuatsi)VHL(scVHL)in the NF-κB signaling pathway and mandarin fish ranavirus(MRV)replication were explored.The transcription of scVHL was induced by immune stimulation and MRV infection,indicating a potential role in innate immunity.Dual-luciferase reporter gene assays and reverse transcription quantitative PCR(RT-qPCR)results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway.Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα,scIKKβ,scIκBα,or scp65.Co-immunoprecipitation(Co-IP)analysis identified scIκBαas a novel target protein of scVHL.Moreover,scVHL targeted scIκBαto catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway.Following MRV infection,NF-κB signaling remained activated,which,in turn,promoted MRV replication.These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication.This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.
