PSMD13 通过靶向 TAK1 进行 K63 链接泛素化来抑制 NF-κB 通路，在米氏绒螯蟹（Miichthys miiuy）中。
PSMD13 inhibits NF-κB pathway by targeting TAK1 for K63-linked ubiquitination in miiuy croaker (Miichthys miiuy).
机构信息
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China; National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, China; Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, China.
出版信息
Fish Shellfish Immunol. 2023 Jul;138:108857. doi: 10.1016/j.fsi.2023.108857. Epub 2023 May 29.
Transforming growth factor-β activated kinase 1 (TAK1) is an adaptor molecular in the TLR-mediated NF-κB pathway which has been implicated in the regulation of a wide range of physiological and pathological processes. Proteasome 26S subunit, non-ATPase (PSMD) 13 is essential for the structural maintenance and function of the 26S proteasome. However, the mechanism of PSMD13 in innate immune regulation is not clear. In this study, the expression of PSMD13 mRNA was significantly increased under Vibrio harveyi stimulation, and PSMD13 inhibited the NF-κB pathway by targeting TAK1. Mechanically, PSMD13 significantly inhibited the K63-linked ubiquitination of TAK1, thereby inhibiting the expression of TAK1. Moreover, this discovery enriches the research of the PSMD family in regulating the innate immune response and provides a new idea for the study of the mammalian innate immune regulation mechanism.
转化生长因子-β激活激酶 1（TAK1）是 TLR 介导的 NF-κB 通路中的衔接分子，参与调节广泛的生理和病理过程。蛋白酶体 26S 亚基，非-ATP 酶（PSMD）13 对于 26S 蛋白酶体的结构维持和功能至关重要。然而，PSMD13 在先天免疫调节中的机制尚不清楚。在这项研究中，在哈维弧菌刺激下，PSMD13 的 mRNA 表达显著增加，并且 PSMD13 通过靶向 TAK1 抑制 NF-κB 通路。在机制上，PSMD13 显著抑制了 TAK1 的 K63 连接泛素化，从而抑制了 TAK1 的表达。此外，这一发现丰富了 PSMD 家族在调节先天免疫反应方面的研究，并为哺乳动物先天免疫调节机制的研究提供了新的思路。
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