E3 ubiquitin ligase ASB8 negatively regulates interferon via regulating TBK1/IKKi homeostasis.

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, I?B 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-?. 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.
Mesh Terms:
HEK293 Cells, HeLa Cells, Humans, I-kappa B Kinase, Immunity, Innate, Interferon Regulatory Factor-3, Interferon Regulatory Factor-7, Interferon-beta, Phosphorylation, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Serine, Signal Transduction, Suppressor of Cytokine Signaling Proteins, Ubiquitin-Protein Ligases, Ubiquitination
Mol Immunol
Date: Dec. 01, 2019
Download Curated Data For This Publication
228350
Switch View:
  • Interactions 14