IRF3 enhances NF-κB activation by targeting IκBα for degradation in teleost fish

Abstract Tightly regulation of NF-κB signaling is essential to innate and adaptive immune responses, but its regulatory mechanism remains unclear in various organisms, especially teleost fish. In this study, we reported that IRF3 attenuates the inhibitory effect of IκBα on NF-κB activation in teleost fish. Overexpression of IRF3 can promote IκBα degradation, whereas its knockdown can relieve degradation of IκBα. IRF3 promoted the degradation of IκBα protein, but this effect could be inhibited by MG132 treatment. IRF3 is crucial for the polyubiquitination and proteasomal degradation of IκBα. Our findings indicate that IRF3 regulates NF-κB pathway by targeting IκBα for ubiquitination and degradation. This study provides novel evidence on the regulation of innate immune signaling pathways in teleost fish and thus provides new insights into the regulatory mechanisms in mammals.