RBCK1 enhances antiviral response through promoting K63-linked polyubiquitination of IRF7 in Carassius auratus var. Pengze

IF 4.1 2区农林科学 Q1 FISHERIES

Fish & shellfish immunology Pub Date : 2025-06-28 DOI:10.1016/j.fsi.2025.110532

Quanling Zhang , Tingting Yu , Zhongwei Wang , Miaomiao Li , Jingen Xu , Xuefeng Liu , Cheng Qian , Zijia Yin , Gang He , Menglei Hu , Binchao Zhang , Jiwei Liu , Zhixin Fu , Shanghong Wang , Xiaowen Xu , Chengyu Hu

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引用次数: 0

Abstract

Ubiquitination is a widely occurring reversible post-translational modification process in cells. RANBP2-type and C3HC4-type zinc finger-containing 1 (RBCK1) is a kind of E3 ubiquitin ligase. It regulates various biological functions, including protein degradation and kinase signaling pathways in mammals. However, the role of RBCK1 in the virus-induced innate immune response remains largely unknown, particularly in teleost. In this study, we demonstrated that the expression of Carassius auratus var Pengze RBCK1 (CapRBCK1) was induced by grass carp reovirus (GCRV) and poly (I:C) stimulation in tissues and cells. CapRBCK1 suppressed the replication of GCRV in cells. Overexpression of CapRBCK1 activated IFN1 response, whereas knockdown of CapRBCK1 inhibited this response. CapRBCK1 is primarily localized in the cytoplasm, where it directly interacted with IRF7 and thereby increased the phosphorylation and dimerization of IRF7 in GCRV-infected cells. Furthermore, CapRBCK1 catalyzed K63-linked ubiquitination of IRF7 at lysine 106. Finally, the mutant of CapRBCK1 RING domain exhibited a significant impairment to IRF7 ubiquitination. So, the RING domain is essential for CapRBCK1 enhancing IFN1 activation. This study provides, to our knowledge, some novel insights into the role of RBCK1 in innate immune response.

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RBCK1通过促进K63-linked IRF7的多泛素化而增强蓬泽鲫的抗病毒应答

泛素化是细胞中广泛发生的可逆的翻译后修饰过程。ranbp2型和c3hc4型含锌指1 （RBCK1）是一种E3泛素连接酶。它调节多种生物功能，包括哺乳动物的蛋白质降解和激酶信号通路。然而，RBCK1在病毒诱导的先天免疫反应中的作用在很大程度上仍然未知，特别是在硬骨鱼中。在本研究中，我们证实了草鱼呼肠孤病毒（GCRV）和poly （I:C）刺激在组织和细胞中诱导aurassius var Pengze RBCK1 （capbck1）的表达。CapRBCK1抑制细胞中GCRV的复制。CapRBCK1过表达激活IFN1反应，而CapRBCK1过表达抑制IFN1反应。capbck1主要定位于细胞质中，在那里它直接与IRF7相互作用，从而增加了gcrv感染细胞中IRF7的磷酸化和二聚化。此外，CapRBCK1在赖氨酸106位点催化了IRF7的k63连锁泛素化。最后，capbck1环结构域突变体对IRF7泛素化表现出明显的损伤。因此，RING结构域对于CapRBCK1增强IFN1激活至关重要。据我们所知，这项研究为RBCK1在先天免疫应答中的作用提供了一些新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fish & shellfish immunology 农林科学-海洋与淡水生物学

CiteScore

7.50

自引率

19.10%

发文量

750

审稿时长

68 days

期刊介绍： Fish and Shellfish Immunology rapidly publishes high-quality, peer-refereed contributions in the expanding fields of fish and shellfish immunology. It presents studies on the basic mechanisms of both the specific and non-specific defense systems, the cells, tissues, and humoral factors involved, their dependence on environmental and intrinsic factors, response to pathogens, response to vaccination, and applied studies on the development of specific vaccines for use in the aquaculture industry.