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Details on Person Viral nucleic acids are sensed by cellular pattern-recogniti...
| Class:Id | Summation:9705332 |
|---|---|
| _displayName | Viral nucleic acids are sensed by cellular pattern-recogniti... |
| _timestamp | 2021-02-17 07:03:32 |
| created | [InstanceEdit:9705319] Shamovsky, Veronica, 2020-10-22 |
| literatureReference | [LiteratureReference:9705315] IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases [LiteratureReference:9705312] Human DEAD box helicase 3 couples IκB kinase ε to interferon regulatory factor 3 activation [LiteratureReference:2408424] IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2 [LiteratureReference:5362581] Crystal structure and mechanism of activation of TANK-binding kinase 1 [LiteratureReference:9705131] Functionally distinct effects of the C-terminal regions of IKKε and TBK1 on type I IFN production [LiteratureReference:2408458] Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation [LiteratureReference:5362611] Structure and ubiquitination-dependent activation of TANK-binding kinase 1 [LiteratureReference:9705074] Evasion of Type I Interferon by SARS-CoV-2 [LiteratureReference:9705328] IKKε-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex [LiteratureReference:9705333] MAVS activates TBK1 and IKKε through TRAFs in NEMO dependent and independent manner [LiteratureReference:166859] IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway [LiteratureReference:9715434] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling |
| modified | [InstanceEdit:9713626] Shamovsky, Veronica, 2021-01-27 [InstanceEdit:9715437] Shamovsky, Veronica, 2021-02-17 |
| text | Viral nucleic acids are sensed by cellular pattern-recognition receptors (PRRs), such as RIG-I-like receptors (RLR). RLRs activate the adaptor protein called mitochondrial antiviral-signaling protein (MAVS). MAVS recruits TBK1 (tumor necrosis factor (TNF) receptor-associated factor (TRAF) family member-associated NF-κB activator (TANK)-binding kinase 1) and/or its close homolog inhibitor-kappa-B kinase (IKK) epsilon (IKKε or IKBKE) via TRAFs (Fitzgerald KA et al. 2003; Fang R et al. 2017). The enzymatic activity of TBK1/IKBKE is initiated by phosphorylation at Ser172 located in the T loop of the TBK1 and IKKε kinase domains, which is essential for the enhancement of kinase activity (Shimada T et al. 1999; Kishore N et al. 2002; Ma X et al. 2012; Gu L et al. 2013). TBK1 forms a homodimer (Larabi A et al. 2013; Tu D et al. 2013) and structural studies suggest that dimerization of TBK1 precludes autophosphorylation and activation in cis (Larabi A et al. 2013). IKBKE is also a dimer (Nakatsu Y et al. 2014). Other kinases such as IKKs were also implicated in TBK1/IKBKE activation (Fang R et al. 2017). Further, K63-linked polyubiquitination on Lys30 and Lys401 enhanced TBK1/IKBKe activation in HEK293 cells (Tu D et al. 2013; Zhou AY et al. 2013). Activated TBK1 and IKBKE (IKKε) in turn trigger phosphorylation of interferon regulatory factor 3 (IRF3) and IRF7 and subsequent expression of type I interferons (IFNs; IFN-α/β). Type I IFNs can induce the expression of numerous antiviral genes called interferon-stimulated genes (ISGs). Many viruses have evolved numerous mechanisms to evade antiviral action of type I IFNs by acting at the level of the TBK1/IKBKE kinases. For example, nonstructural protein 13 (nsp13) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) binds and blocks TBK1 phosphorylation, while nsp6 binds TBK1 to suppress TBK1-mediated phosphorylation of IRF3 (Xia H et al. 2020). SARS-CoV-2 membrane protein M interacts with MAVS and TBK1 thus preventing the formation of MAVS signalosome (Zheng Y et al. 2020). |
| (summation) | [Reaction:9705320] TBK1, IKBKE are autophosphorylated at Ser172 [Homo sapiens] |
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