IRF3 enhances NF-kappa B activation by targeting I kappa B alpha for degradation in teleost fish

摘要

Tightly regulation of NF-kappa B 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 I kappa B alpha on NF-kappa B activation in teleost fish. Overexpression of IRF3 can promote I kappa B alpha degradation, whereas its knockdown can relieve degradation of I kappa B alpha. IRF3 promoted the degradation of I kappa B alpha protein, but this effect could be inhibited by MG132 treatment. IRF3 is crucial for the polyubiquitination and proteasomal degradation of I kappa B alpha. Our findings indicate that IRF3 regulates NF-kappa B pathway by targeting I kappa B alpha 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.