斑马鱼 SETD3 介导的磷酸蛋白泛素化限制了鲤鱼疱疹病毒的感染。
Zebrafish SETD3 mediated ubiquitination of phosphoprotein limits spring viremia of carp virus infection.
机构信息
Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China.
Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266200, China.
出版信息
Fish Shellfish Immunol. 2023 Aug;139:108870. doi: 10.1016/j.fsi.2023.108870. Epub 2023 Jun 1.
Lysine methylation is a post-translational modification of histone and non-histone proteins and affects numerous cellular processes. The actin histidine methyltransferase SET domain containing 3 (SETD3) is a member of the protein lysine methyltransferase (PKMT) family which catalyse the addition of methyl groups to lysine residues. However, the role of SETD3 in virus-mediated innate immune responses has rarely been investigated. In this study, zebrafish SETD3 was shown to be induced by poly(I:C) and spring viremia of carp virus (SVCV) and inhibited virus infection. Further, it was found that SETD3 directly interacted with SVCV phosphoprotein (SVCV P) in the cytoplasm of EPC cells, initiating ubiquitination to degrade the SVCV P protein via proteasomal pathway. Interestingly, mutants lacking the SET and RSB domains were able to promote degradation of SVCV P, indicating that they are not required for SETD3 mediated degradation of SVCV P. Taken together, our study demonstrates that SETD3 is an antiviral factor which limits virus replication by promoting ubiquitination of viral phosphoprotein and subsequent protein degradation.
赖氨酸甲基化是组蛋白和非组蛋白蛋白质的一种翻译后修饰，影响众多细胞过程。肌动蛋白组氨酸甲基转移酶 SET 结构域包含 3（SETD3）是蛋白赖氨酸甲基转移酶（PKMT）家族的成员，其催化赖氨酸残基上甲基的添加。然而，SETD3 在病毒介导的先天免疫反应中的作用很少被研究。在这项研究中，斑马鱼 SETD3 被证明可以被聚（I：C）和鲤鱼春病毒血症病毒（SVCV）诱导，并抑制病毒感染。此外，还发现 SETD3 直接在 EPC 细胞的细胞质中与 SVCV 磷蛋白（SVCV P）相互作用，通过蛋白酶体途径引发泛素化降解 SVCV P 蛋白。有趣的是，缺乏 SET 和 RSB 结构域的突变体能够促进 SVCV P 的降解，表明它们对于 SETD3 介导的 SVCV P 降解不是必需的。总之，我们的研究表明，SETD3 是一种抗病毒因子，通过促进病毒磷蛋白的泛素化和随后的蛋白降解来限制病毒复制。
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