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-kappa B signaling pathway and plays indispensable roles in innate immunity. As the most typical innate immune pathway, the strict regulation of NF-kappa B signaling pathway is particularly important. Rho-GDP-dissociation inhibitor-gamma (Rho-GDI gamma) 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-GDI gamma negatively regulated the NF-kappa B signaling pathway mediated by TAK1. We determined that TAK1 could directly interact with Rho-GDI gamma. It is interesting that Rho-GDI gamma 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.

Automated summary

This study demonstrates the mechanism of how Rho-GDI γ negatively regulates the NF-κB signaling pathway mediated by TAK1, providing new experimental and theoretical basis for the innate immune regulation in teleost fish and mammals.