E3 ubiquitin ligase ASB8 negatively regulates interferon via regulating TBK1/IKKi homeostasis
- Mol Immunol. 2020 May:121:195-203. doi: 10.1016/j.molimm.2020.03.011.
- 1. School of Life Sciences, Tianjin University, Tianjin, 300072, China.
- 2. School of Life Sciences, Tianjin University, Tianjin, 300072, China. Electronic address: [email protected].
Cells recognize virus nucleic acid by Pattern Recognition Receptors (PRRs), virus involve in the activation of signaling cascade of variable adaptor proteins, TANK-binding kinase1(TBK1)/ inhibitor of nuclear factor kappa-B kinase subunit epsilon(IKKi) complex, IκB kinase(IKKs) to trigger activation of transcription factor, interferon regulatory factor 3/7(IRF3/7), ultimately, leading to the production of type I interferon and exert anti-viral effects. In this study, E3 ubiquitin Ligase ankyrin repeat and SOCS box-containing 8(ASB8) interacted with TBK1/IKKi and phosphorylation modification of ASB8 at site of Ser17 to further strengthen its ubiquitination activity were verified. Conversely, phosphorylated ASB8 accelerate K48-linked ubiquitination and degradation of TBK1/IKKi, which further reduces phosphorylation level of IRF3 and inhibits production of IFN-β. At the same time, a new bridge molecule Leucine-rich repeat containing protein 10B(LRRC10B) upregulated after Viral Infection are involved in the formation and interaction with ASB8-TBK1/IKKi complex was reported. Our study reveals a new mechanism of ubiquitin Ligase ASB8 modulating Antiviral innate immunity by altering stability of TBK1/IKKi kinase complex.