普通话鱼von hippel-lindau蛋白通过与IκB的相互作用调节NF-κB信号通路以促进鱼兰科病毒复制
Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication
影响因子:4.70000
分区:生物学1区 Top / 动物学1区
发表日期:2024 Sep 18
作者:
Zhi-Min Li, Xiao-Wei Qin, Qi Zhang, Jian He, Min-Cong Liang, Chuan-Rui Li, Yang Yu, Weng-Hui Liu, Shao-Ping Weng, Jian-Guo He, Chang-Jun Guo
摘要
von Hippel-Lindau肿瘤抑制蛋白（VHL）是E3泛素连接酶，是靶向低氧诱导因子的氧气感应途径的关键调节剂。最近的证据表明，尽管特定的分子机制尚不清楚，但哺乳动物VHL也可能对NF-κB信号通路至关重要。在此，探索了探索探索NF-κB信号通路和普通话鱼兰纳维病毒（MRV）复制的普通话鱼（Siniperca chuatsi）VHL（SCVHL）的作用。 SCVHL的转录是通过免疫刺激和MRV感染诱导的，表明在先天免疫中具有潜在的作用。双雷酸酶报告基因测定和逆转录定量PCR（RT-QPCR）结果表明，SCVHL引起并积极调节NF-κB信号传导途径。 NF-κB信号通路途径抑制剂的处理表明，SCVHL的作用可以通过Scikkα，Scikkβ，SciκBα或SCP65介导。共免疫沉淀（CO-IP）分析确定SCIκBα是SCVHL的新型靶蛋白。此外，SCVHL靶向SCIκBα以催化K63连接的多泛素链的形成以激活NF-κB信号通路。 MRV感染后，NF-κB信号仍然被激活，这又促进了MRV复制。这些发现表明，SCVHL不仅对NF-κB进行了积极调节，而且显着增强了MRV复制。这项研究揭示了SCVHL在FISH中NF-κB信号传导和病毒感染中的新功能。
Abstract
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 scIκBα as a novel target protein of scVHL. Moreover, scVHL targeted scIκBα to 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.