Rho-GDP-dissociation inhibitor-γ negatively regulates NF-κB signaling by promoting the degradation of TAK1 in miiuy croaker (Miichthys miiuy).

Transforming growth factor-beta activated kinase 1 (TAK1) is an adaptor molecular in TLR-mediated NF-κB signaling pathway and plays indispensable roles in innate immunity. As the most typical innate immune pathway, the strict regulation of NF-κB signaling pathway is particularly important. Rho-GDP-dissociation inhibitor-γ (Rho-GDIγ) is a member of the Rho protein family that regulates many important physiological processes. In this study, we demonstrated the mechanism of suppressing TAK1 expression in the teleost and found that Rho-GDIγ negatively regulated the NF-κB signaling pathway mediated by TAK1. We determined that TAK1 could directly interact with Rho-GDIγ. It is interesting that Rho-GDIγ promotes TAK1 degradation through the ubiquitin proteasome pathway. This study brings a new experimental basis to the teleost fish innate immune signaling pathway. Moreover, this discovery may provide new insights into innate immune regulation mechanism in mammals.