{Reference Type}: Journal Article
{Title}: Black carp A20 inhibits interferon signaling through de-ubiquitinating IKKβ.
{Author}: Yang X;Xie L;Yin Y;Yang C;Xiao J;Wu H;Wang C;Tian Y;Feng H;
{Journal}: Fish Shellfish Immunol
{Volume}: 152
{Issue}: 0
{Year}: 2024 Sep 18
{Factor}: 4.622
{DOI}: 10.1016/j.fsi.2024.109781
{Abstract}: IkappaB kinase beta (IKKβ) is a key member of IκB kinases and functions importantly in interferon (IFN) signaling. Phosphorylation and ubiquitination are involved in the activation of IKKβ. A20 is a de-ubiquitin enzyme and functions as a suppressor in inflammation signaling, which has been reported to be phosphorylated and activated by IKKβ. However, the role and relationship of IKKβ and A20 in teleost remains unclear. In this study, IKKβ (bcIKKβ) and A20 (bcA20) of black carp (Mylopharyngodon piceus) have been cloned and characterized. Overexpressed bcIKKβ in EPC cells showed strong anti-viral ability by activating both NF-κB and IFN signaling. EPC cells stable expressing bcIKKβ presented improved anti-viral activity as well. The interaction between bcA20 and bcIKKβ was identified, and overexpression of bcA20 was able to suppress bcIKKβ-mediated activation of NF-κB and IFN signaling. Meanwhile, knock-down of A20 increased host the antiviral ability of host cells. Importantly, it has been identified that bcA20 was able to remove K27-linked ubiquitination and decrease the phosphorylation of bcIKKβ. Thus, our data conclude that bcA20 suppresses the anti-viral activity of bcIKKβ and removes its K27-linked ubiquitination, which presents a new mechanism of IKKβ regulation.