Journal
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
Volume 135, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.dci.2022.104496
Keywords
Rho-GDI ?; TAK1; NF; ?B signaling pathway; Ubiquitin-proteasome
Categories
Funding
- National Key Research and Devel- opment Project
- National Nature Science Foundation of China
- [2018YFD0900503]
- [31822057]
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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.
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.
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