RNF8 Inhibits TNF α-induced NF-κ B Activation & AIMP2 Promotes IAV Replication By Binding To NS2

NF-κB is a critical regulator of innate immunity, stress resonses, cell differentiation and apoptosis. The activation of NF-κB signaling pathway could be triggered by a wide variety of factors, which in turn mediates transcriptional programs. Here, we present data that overexpression of RNF8 could significantly inhibit TNF-a-induced NF-κB activation and nuclear translocation of p65. RNF8 directly associates with IKKα/β and TAK1, and they are co-localized in cytoplasm. RING domain of RNF8 is essential for binding with TAK1. Interaction of RNF8 with TAK1 promotes RNF8 to function as an E3 ligase to mediate K48-linked polyubiquitination and degradation of TAB2, and thereby negatively regulates NF-κB signaling pathway. Collectively, these results demonstrate that RNF8 acts as a negative regulator of NF-κB signaling pathway, which shed light on a new understanding of regulation of NF-κB signaling pathway in innate immunity.Influenza A viruses (IAV) hijacks cellular machinery or interacts with cellular proteins to support their life cycle. Thus, identification and characterization of the interaction between viral components and host factors would help us understand the mechanisms by which viruses cause pandemic potential. We previously identified that IAV NS2 protein interacted with AIMP2 and facilitaeted IAV replication. Here, we present data that IAV infection promotes ubiquitination and degradation of AIMP2. Interaction with NS2 protects AIMP2 from proteasome-mediated degradation. AIMP2 functions as a positive regulator of IAV replication by promoting vRNP nuclear export. AIMP2 could increase M1 protein levels during IAV infection. M1 and NS2 are key regulators of vRNP nuclear export. AIMP2 promotes IAV replication by enhancing the stability of M1. Our study provides a new mechanism used by IAV for supporting its life cycle.