Nucleoporin 43 inhibits NF-κB pathway by targeting TRAF6 in miiuy croaker, Miichthys miiuy

Abstract

Tumor necrosis factor receptor-associated factor 6 (TRAF6) serves as a critical factor in the initiation of the NF-κB pathway and holds significance in modulating the inflammatory response. However, the regulatory mechanism of TRAF6 in teleost fish is poorly understood. We demonstrate Miichthys miiuy nucleoporin 43 (mm-nup43), a member of the nuclear pore complex (NPC), is a negative regulator of the NF-κB pathway and inhibits the expression of inflammatory cytokines. Mechanistically, mm-nup43 interacts with TRAF6 and inhibits it via the ubiquitin-proteasome pathway. Meanwhile, mm-nup43 decreased p65 phosphorylation, thereby negatively regulating NF-κB signaling. In summary, these results classify that mm-nup43 inhibits the TRAF6-mediated NF-κB pathway and prevents excessive inflammation.