E3 ubiquitin ligase ASB8 negatively regulates interferon via regulating TBK1/IKKi homeostasis. (May 2020)

• Record Type: Journal Article
• Authors: Guo, Yanyu; Li, Ruiqiao; Tan, Zheng; Shi, Jingxuan; Fu, Yali; Song, Yinna; Zhu, Min; Zhang, Lei; Huang, Jinhai
• Is Part Of: Molecular immunology. Volume 121(2020:May)
• Page Start: 195
• Page End: 203
• Publication Date: 2020-05
• Subjects: Ankyrin repeat and SOCS box–containing 8 (ASB8) -- TANK-binding kinase1 (TBK1) -- Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKi) -- Leucine-rich repeat containing protein 10B(LRRC10B) -- Ubiquitination -- Phosphorylation; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2020.03.011
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: E3 ubiquitin ligase ASB8 interacts with TBK1/IKKi were founded. ASB8 accelerate K48-linked ubiquitination TBK1/IKKi to inhibit IFN-β production. A new bridge molecule LRRC10B involving in formation and homeostasis of ASB8-TBK1/IKKi complex. Abstract: 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.