Immunobiology for Aquaculture Group, Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain.
Centro Oceanográfico de Murcia, Instituto Español de Oceanografía (COMU-IEO), CSIC Carretera de la Azohía s/n, Puerto de Mazarrón, 30860 Murcia, Spain.
Int J Mol Sci. 2024 Jul 15;25(14):7751. doi: 10.3390/ijms25147751.
E3 ubiquitin ligases, key components of the ubiquitin proteasome system, orchestrate protein degradation through ubiquitylation and profoundly impact cellular biology. Small HERC E3 ligases (HERC3-6) have diverse functions in mammals, including roles in spermatogenesis, protein degradation, and immunity. Until now, only mammals' HERC3, HERC5, and HERC6 are known to participate in immune responses, with major involvement in the antiviral response. Interestingly, an exclusive HERC7 has been characterized in fish showing great molecular conservation and antiviral roles. Thus, this study identifies and characterizes the gene in the European sea bass teleost. The European sea bass gene and the putative protein show good conservation of the promoter binding sites for interferons and the RCC1 and HECT domains characteristic of HERC proteins, respectively. The phylogenetic analysis shows a unique cluster with the fish-exclusive HERC7 orthologues. During ontogeny, the gene is expressed from 3 days post-fertilization onwards, being constitutively and widely distributed in adult tissues. In vitro, stimulated leucocytes up-regulate the gene in response to mitogens and viruses, pointing to a role in the immune response. Furthermore, sea bass expression is related to the interferon response intensity and viral load in different tissues upon in vivo infection with red-grouper betanodavirus (RGNNV), suggesting the potential involvement of fish HERC7 in ISGylation-based antiviral activity, similarly to mammalian HERC5. This study broadens the understanding of small HERC proteins in fish species and highlights HERC7 as a potential contributor to the immune response in European sea bass, with implications for antiviral defense mechanisms. Future research is needed to unravel the precise actions and functions of HERC7 in teleost fish immunity, providing insights into direct antiviral activity and viral evasion.
E3 泛素连接酶是泛素蛋白酶体系统的关键组成部分，通过泛素化来协调蛋白质降解，对细胞生物学产生深远影响。小型 HERC E3 连接酶（HERC3-6）在哺乳动物中具有多种功能，包括在精子发生、蛋白质降解和免疫中发挥作用。到目前为止，只有哺乳动物的 HERC3、HERC5 和 HERC6 被认为参与免疫反应，主要涉及抗病毒反应。有趣的是，鱼类中已经鉴定出一种独特的 HERC7，其具有高度的分子保守性和抗病毒作用。因此，本研究在鲈形目鱼类中鉴定和表征了 基因。欧洲鲈鱼 基因和假定蛋白分别显示出干扰素启动子结合位点和 RCC1 和 HECT 结构域的良好保守性，这些特征是 HERC 蛋白的特征。系统发育分析显示出一个与鱼类特有的 HERC7 同源物的独特聚类。在个体发生过程中，该基因从受精后 3 天开始表达，在成年组织中持续广泛表达。在体外，刺激的白细胞在受到有丝分裂原和病毒刺激时会上调 基因的表达，表明其在免疫反应中发挥作用。此外，在体内感染红鳍东方鲀虹彩病毒（RGNNV）后，鲈鱼 表达与干扰素反应强度和不同组织中的病毒载量相关，这表明鱼类 HERC7 可能参与了基于 ISGylation 的抗病毒活性，类似于哺乳动物 HERC5。本研究拓宽了对鱼类中小型 HERC 蛋白的理解，并强调了 HERC7 作为欧洲鲈鱼免疫反应的潜在贡献者，这对抗病毒防御机制具有重要意义。未来的研究需要揭示 HERC7 在硬骨鱼类免疫中的精确作用和功能，为直接抗病毒活性和病毒逃避提供深入了解。
