PDF(Pubmed)
Abstract：
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 herc7 gene in the European sea bass teleost. The European sea bass herc7 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 herc7 gene is expressed from 3 days post-fertilization onwards, being constitutively and widely distributed in adult tissues. In vitro, stimulated leucocytes up-regulate the herc7 gene in response to mitogens and viruses, pointing to a role in the immune response. Furthermore, sea bass herc7 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.
摘要：
E3泛素连接酶，泛素蛋白酶体系统的关键成分，通过泛素化协调蛋白质降解并深刻影响细胞生物学。小HERCE3连接酶（HERC3-6）在哺乳动物中具有不同的功能，包括在精子发生中的作用，蛋白质降解，和豁免权。直到现在,已知只有哺乳动物HERC3，HERC5和HERC6参与免疫反应，主要参与抗病毒反应。有趣的是,一种独特的HERC7在鱼类中表现出良好的分子保守性和抗病毒作用。因此，这项研究鉴定并表征了欧洲鲈鱼硬骨鱼中的herc7基因。欧洲鲈鱼herc7基因和推定的蛋白质显示出干扰素的启动子结合位点以及HERC蛋白质特征性的RCC1和HECT结构域的良好保守性，分别。系统发育分析显示了具有鱼类专有HERC7直向同源物的独特簇。在个体发育期间，herc7基因从受精后3天开始表达，在成体组织中广泛分布。体外，刺激的白细胞上调herc7基因，以响应有丝分裂原和病毒，指向在免疫反应中的作用。此外，鲈鱼herc7的表达与体内感染红石斑鱼betanodavirus（RGNNV）后不同组织中的干扰素反应强度和病毒载量有关，表明鱼类HERC7可能参与基于ISGylation的抗病毒活性，类似于哺乳动物HERC5。这项研究扩大了对鱼类中小HERC蛋白的理解，并强调了HERC7是欧洲鲈鱼免疫反应的潜在贡献者。对抗病毒防御机制的影响。需要未来的研究来揭示HERC7在硬骨鱼免疫中的精确作用和功能，提供对直接抗病毒活性和病毒逃避的见解。
