鳜鱼von Hippel-Lindau蛋白通过与IκB相互作用调节NF-κB信号通路,从而促进鱼类Ranavirus的复制。

IF 4 1区 生物学 Q1 ZOOLOGY Zoological Research Pub Date : 2024-09-18 DOI:10.24272/j.issn.2095-8137.2023.392
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
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引用次数: 0

摘要

Von Hippel-Lindau肿瘤抑制蛋白(VHL)是一种E3泛素连接酶,是氧传感通路的关键调节因子,可靶向缺氧诱导因子。最近的证据表明,哺乳动物的 VHL 也可能是 NF-κB 信号通路的关键,但具体的分子机制仍不清楚。本文探讨了鳜鱼VHL(scVHL)在NF-κB信号通路和鳜鱼病毒(MRV)复制中的作用。scVHL的转录受免疫刺激和MRV感染的诱导,表明其在先天性免疫中的潜在作用。双荧光素酶报告基因检测和反转录定量 PCR(RT-qPCR)结果表明,scVHL 可诱导并正向调节 NF-κB 信号通路。用NF-κB信号通路抑制剂处理表明,scVHL的作用可能是通过scIKKα、scIKKβ、scIκBα或scp65介导的。共免疫沉淀(Co-IP)分析发现,scIκBα是scVHL的一种新型靶蛋白。此外,scVHL以scIκBα为靶蛋白,催化K63连接的多泛素链的形成,从而激活NF-κB信号通路。MRV感染后,NF-κB信号仍处于激活状态,这反过来又促进了MRV的复制。这些发现表明,scVHL 不仅能正向调节 NF-κB,还能显著增强 MRV 复制。这项研究揭示了scVHL在鱼类NF-κB信号传导和病毒感染中的新功能。
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Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication.

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.

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来源期刊
Zoological Research
Zoological Research Medicine-General Medicine
CiteScore
7.60
自引率
10.20%
发文量
1937
审稿时长
8 weeks
期刊介绍: Established in 1980, Zoological Research (ZR) is a bimonthly publication produced by Kunming Institute of Zoology, the Chinese Academy of Sciences, and the China Zoological Society. It publishes peer-reviewed original research article/review/report/note/letter to the editor/editorial in English on Primates and Animal Models, Conservation and Utilization of Animal Resources, and Animal Diversity and Evolution.
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