IRF1 negatively regulates NF-κB signaling by targeting MyD88 for degradation in teleost fish

Abstract

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.