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

Ye, Jung Sook; Kim, Nari; Lee, Kyung Jin; Nam, Young Ran; Lee, Uk; Joo, Chul Hyun

doi:10.1128/jvi.02037-14

Cited by 47 publications

(30 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ubiquitination of many other proteins of the RLR signaling pathway has been reported (Gack et al, 2007; Liu et al, 2013; Maelfait and Beyaert, 2012; Tu et al, 2013; Ye et al, 2014); the nature of the ubiquitination linkages on most of these proteins is either K48-linked branches, leading to proteolytic degradation of the target protein, or K63-linked branches leading to its activation in signal transduction (Nakhaei et al, 2009; Zeng et al, 2009). Although degradative ubiquitination of IRF-3 has been described before (Chen et al, 2007; Yu and Hayward, 2010; Zhang et al, 2008), our analysis of RIPA provided an example of activating ubiquitination of IRF-3.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitination of the Transcription Factor IRF-3 Activates RIPA, the Apoptotic Pathway that Protects Mice from Viral Pathogenesis

et al. 2016

View full text Add to dashboard Cite

SUMMARY The transcription factor IRF-3 mediates cellular antiviral response by inducing the expression of interferon and other antiviral proteins. In RNA-virus infected cells, IRF-3’s transcriptional activation is triggered primarily by RIG-I-like receptors (RLR), which can also activate the RLR-induced IRF-3-mediated pathway of apoptosis (RIPA). Here, we have reported that the pathway of IRF-3 activation in RIPA was independent of and distinct from the known pathway of transcriptional activation of IRF-3. It required linear polyubiquitination of two specific lysine residues of IRF-3 by LUBAC, the linear polyubiquitinating enzyme complex, which bound IRF-3 in signal-dependent fashion. To evaluate the role of RIPA in viral pathogenesis, we engineered a genetically targeted mouse, which expressed a mutant IRF-3 that was RIPA-competent but transcriptionally inert; this single-action IRF-3 could protect mice from lethal viral infection. Our observations indicated that IRF-3-mediated apoptosis of virus-infected cells could be an effective antiviral mechanism, without expression of the interferon-stimulated genes.

show abstract

Section: Discussionmentioning

confidence: 99%

Ubiquitination of the Transcription Factor IRF-3 Activates RIPA, the Apoptotic Pathway that Protects Mice from Viral Pathogenesis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Detailed analysis demonstrated that TBK1 ubiquitination by MIBs was critical for the recruitment of NEMO and the antiviral response triggered by cytosolic viral RNA [153, 154]. Mechanistically, MIB2 was shown to bind to the adaptor MAVS involving a highly conserved DLAIS motif at amino acid positions 438 to 442 of MAVS; this motif was critical for MIB2-mediated TBK1 ubiquitination and subsequent IRF3/7 phosphorylation by TBK1 [155]. Furthermore, TRAF3 and Nrdp1 have also been shown to mediate TBK1 K63-linked ubiquitination [100, 156].…”

Section: Ubiquitin-dependent Regulation Of Common Downstream Signalinmentioning

confidence: 99%

Ubiquitination in the antiviral immune response

2015

View full text Add to dashboard Cite

Ubiquitination has long been known to regulate fundamental cellular processes through the induction of proteasomal degradation of target proteins. More recently, ‘atypical’ nondegradative types of polyubiquitin chains have been appreciated as important regulatory moieties by modulating the activity or subcellular localization of key signaling proteins. Intriguingly, many of these non-degradative types of ubiquitination regulate the innate sensing pathways initiated by pattern recognition receptors (PRRs), ultimately coordinating an effective antiviral immune response. Here we discuss recent advances in understanding the functional roles of degradative and atypical types of ubiquitination in innate immunity to viral infections, with a specific focus on the signaling pathways triggered by RIG-I-like receptors, Toll-like receptors, and the intracellular viral DNA sensor cGAS.

show abstract

“…K48 and K63, the lysines at positions 48 and 63 of ubiquitin linked with polyubiquitin chains, are two canonical polyubiquitin chain linkages. A series of cases have reported that the target proteins were degraded by K48-linked polyubiquitin chains in a proteasome-dependent manner, whereas their functions were stabilized and enhanced by K63-linked polyubiquitin chains (35)(36)(37). To dissect the pattern of ubiquitination of MAVS through K48-or K63-linked ubiquitination, cells were cotransfected with MAVS-Flag, Myc-N, HA-Ub-K48O, or HA-Ub-K63O.…”

Section: N Protein Promotes Ubiquitination Of Mavsmentioning

confidence: 99%

Spring Viremia of Carp Virus N Protein Suppresses Fish IFNφ1 Production by Targeting the Mitochondrial Antiviral Signaling Protein

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

For a virus to replicate efficiently, it must try and inhibit host IFN expression because IFN is an important host defense at early stages after viral infection. For aquatic viruses, the mechanisms used to escape the hosts IFN system are still unclear. In this study, we show that the N protein of spring viremia of carp virus (SVCV) inhibits zebrafish IFNφ1 production by degrading the mitochondrial antiviral signaling protein (MAVS). First, the upregulation of IFNφ1 promoter activity stimulated by polyinosinic:polycytidylic acid, retinoic acid–inducible gene I (RIG-I) or MAVS was suppressed by the SVCV infection. However, the upregulation by the downstream factor of the RIG-I–like receptor signaling pathway, TANK-binding kinase 1, was not affected. Notably, at the protein level, MAVS decreased remarkably when cells were infected with SVCV. Second, consistent with the result of the SVCV infection, overexpression of the N protein of SVCV blocked the IFNφ1 transcription activated by MAVS and downregulated MAVS expression at the protein level but not at the mRNA level. Further analysis demonstrated that the N protein targeted MAVS for K48-linked ubiquitination, which promoted the degradation of MAVS. These data indicated that fish MAVS could be degraded by the N protein of SVCV through the ubiquitin-proteasome pathway. To our knowledge, this is the first article of a fish RIG-I–like receptor pathway interfered by an aquatic virus in an ubiquitin-proteasome manner, suggesting that immune evasion of a virus also exists in lower vertebrates.

show abstract

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

Cited by 47 publications

References 43 publications

Ubiquitination of the Transcription Factor IRF-3 Activates RIPA, the Apoptotic Pathway that Protects Mice from Viral Pathogenesis

Ubiquitination of the Transcription Factor IRF-3 Activates RIPA, the Apoptotic Pathway that Protects Mice from Viral Pathogenesis

Ubiquitination in the antiviral immune response

Spring Viremia of Carp Virus N Protein Suppresses Fish IFNφ1 Production by Targeting the Mitochondrial Antiviral Signaling Protein

Contact Info

Product

Resources

About