Lysine 63-Linked TANK-Binding Kinase 1 Ubiquitination by Mindbomb E3 Ubiquitin Protein Ligase 2 Is Mediated by the Mitochondrial Antiviral Signaling Protein

• DOI: 10.1128/jvi.02037-14
• Publication Date: 2014-08-21T06:52:11Z
• Authors: Jung Sook Ye; Nari Kim; Kyoung Jin Lee; Young Ran Nam; Uk Lee; Chul Hyun Joo
• Keywords: IRF3; IRF7

ABSTRACT Beta interferon (IFN-β) is involved in a wide range of cellular functions, and its secretion must be tightly controlled to inhibit viral spreading while minimizing damage. Intracellular replication triggers signaling cascades leading the activation transcription factors NF-κB regulatory factor 3 (IRF3) IRF7 (IRF3/7), which synergistically bind IFN-β gene promoter induce expression. The mitochondrial antiviral protein (MAVS) governing adaptor that mediates communications between virus-sensing proteins factors. activity MAVS regulation affected by many However, mechanism MAVS-mediated IRF3/7 not completely understood. Here, we identified highly conserved DLAIS motif at amino acid positions 438 442 indispensable for activation. Specifically, L439S A440R mutations suppress Pulldown experiments using wild-type mutant showed mindbomb E3 ubiquitin ligase 2 (MIB2) binds motif. Furthermore, was found critical MIB2 binding, ligation K63-linked TANK-binding kinase 1, phosphorylation-mediated Our results suggest plays putative role signaling. IMPORTANCE Mitochondrial from induction beta interferon. underlying 7 (IRF3/7) We through 1 (TBK1) it as binding site (MIB2). targeted abolished attenuated ubiquitination TBK1, decreased IRF3/7.