MyD88 is considered as one of the most crucial adaptors in TLR signaling pathway. MyD88 may be influential to interferon regulatory factors (IRFs), while the way that IRFs regulate MyD88 is not fully understood. In this study, we demonstrated that the member of IRF family named IRF1 in miiuy croaker played a role as a negative regulator of MyD88-mediated NF-κB signaling and promoted the degradation of MyD88. Firstly, we found the strong inhibitory effect of IRF1 on MyD88-mediated NF-κB signaling pathway. Secondly, we confirmed that IRF1 could enhance the degradation of MyD88, while the knockdown of IRF1 presented an opposite result. Furthermore, the DBD domain of IRF1 was necessary for the inhibition to MyD88. In addition, it could be found that IRF1 could promote MyD88 degradation through ubiquitin-proteasome pathway. Our findings suggest that miiuy croaker IRF1 negatively regulates the cellular response by targeting MyD88 for degradation, which provides new insights into the regulatory mechanism in teleost.

中文翻译：

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IRF1 通过靶向 MyD88 在硬骨鱼中降解来负调节 NF-κB 信号。

MyD88 被认为是 TLR 信号通路中最重要的接头之一。MyD88 可能对干扰素调节因子 (IRF) 有影响，而 IRF 调节 MyD88 的方式尚不完全清楚。在这项研究中，我们证明了在 miiuy croaker 中名为 IRF1 的 IRF 家族成员作为 MyD88 介导的 NF-κB 信号传导的负调节因子发挥了作用，并促进了 MyD88 的降解。首先，我们发现 IRF1 对 MyD88 介导的 NF-κB 信号通路有很强的抑制作用。其次，我们证实IRF1可以增强MyD88的降解，而IRF1的敲低则呈现相反的结果。此外，IRF1 的 DBD 结构域是抑制 MyD88 所必需的。此外，可以发现IRF1可以通过泛素-蛋白酶体途径促进MyD88降解。