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Details on Person E3 ubiquitin-protein ligase RNF128 co-immunoprecipitates wit...
| Class:Id | Summation:9729887 |
|---|---|
| _displayName | E3 ubiquitin-protein ligase RNF128 co-immunoprecipitates wit... |
| _timestamp | 2021-05-07 14:02:51 |
| created | [InstanceEdit:9729888] Shamovsky, Veronica, 2021-05-04 |
| literatureReference | [LiteratureReference:9729658] E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1 [LiteratureReference:5362611] Structure and ubiquitination-dependent activation of TANK-binding kinase 1 [LiteratureReference:166859] IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway [LiteratureReference:9705328] IKKε-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex |
| modified | [InstanceEdit:9730422] Shamovsky, Veronica, 2021-05-07 |
| text | E3 ubiquitin-protein ligase RNF128 co-immunoprecipitates with serine/threonine-protein kinase TBK1 upon co-expression in human embryonic kidney (HEK293) cells (Song G et al. 2016). An interaction between endogenous RNF128 and TBK1 was detected in mouse peritoneal macrophages and human monocyte-like THP-1 cells. Co-expression of domain-deleted mutants of RNF128 with TBK1 in HEK293 cells demonstrated that RNF128 binds TBK1 through its protease-associated (PA) domain (Song G et al. 2016). Mutagenesis analysis showed that RNF128 catalyzes K63-linked polyubiquitination of TBK1 at Lys30 and Lys401 (Song G et al. 2016). Structural studies revealed that dimer formation and K63-linked polyubiquitination of TBK1 at Lys30 and Lys401 are required for TBK1 activation (Tu D et al. 2013). Similar findings were reported for the close homolog IKBKE (Zhou AY et al. 2013). Activated TBK1 and IKBKE in turn phosphorylate the transcription factors IRF3 and IRF7 to induce type I interferon (IFN) production (Fitzgerald KA et al. 2003). In human and mouse cells, knockdown of RNF128 expression with siRNA increased replication of vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) and attenuated production and signaling of IFN-β in response to poly(I:C), Sendai virus (SeV), interferon-stimulatory DNA (ISD), and HSV-1. Similar results were observed for peritoneal macrophages from Rnf128-/- mice. Activation of TBK1 was also decreased in SeV- and HSV-1-induced Rnf128-/- macrophages. Further, Rnf128-/- mice showed higher mortality than wild-type mice upon infection with VSV or HSV-1 (Song G et al. 2016). The data suggest that RNF128 positively regulates antiviral immune responses to RNA and DNA viruses by promoting K63-linked polyubiquitination of TBK1 downstrean of Toll-like receptor 3 (TLR3) and RIG-I-like receptors (RLR) signaling pathways (Song G et al. 2016). This Reactome event shows RNF128-mediated conjugation of K63-linked ubiquitin chains to TBK1. |
| (summation) | [BlackBoxEvent:9729623] RNF128 polyubiquitinates TBK1 [Homo sapiens] |
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