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PMID:22945920
| Citation |
Zhang, M, Wang, L, Zhao, X, Zhao, K, Meng, H, Zhao, W and Gao, C (2012) TRAF-interacting protein (TRIP) negatively regulates IFN-β production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1. J. Exp. Med. 209:1703-11 |
|---|---|
| Abstract |
TANK-binding kinase 1 (TBK1) plays an essential role in Toll-like receptor (TLR)- and retinoic acid-inducible gene I (RIG-I)-mediated induction of type I interferon (IFN; IFN-α/β) and host antiviral responses. How TBK1 activity is negatively regulated remains largely unknown. We report that TNF receptor-associated factor (TRAF)-interacting protein (TRIP) promotes proteasomal degradation of TBK1 and inhibits TLR3/4- and RIG-I-induced IFN-β signaling. TRIP knockdown resulted in augmented activation of IFN regulatory factor 3 (IRF3) and enhanced expression of IFN-β in TLR3/4- and RIG-I-activated primary peritoneal macrophages, whereas overexpression of TRIP had opposite effects. Consistently, TRIP impaired Sendai virus (SeV) infection-induced IRF3 activation and IFN-β production and promoted vesicular stomatitis virus (VSV) replication. As an E3 ubiquitin ligase, TRIP negatively regulated the cellular levels of TBK1 by directly binding to and promoting K48-linked polyubiquitination of TBK1. Therefore, we identified TRIP as a negative regulator in TLR3/4- and RIG-I-triggered antiviral responses and suggested TRIP as a potential target for the intervention of diseases with uncontrolled IFN-β production. |
| Links |
PubMed PMC3457734 Online version:10.1084/jem.20120024 |
| Keywords |
Animals; Cell Line; Gene Expression Regulation; Humans; Interferon Regulatory Factor-3/genetics; Interferon Regulatory Factor-3/metabolism; Interferon-beta/biosynthesis; Macrophages, Peritoneal/metabolism; Macrophages, Peritoneal/virology; Membrane Proteins/metabolism; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins/metabolism; Proteasome Endopeptidase Complex/metabolism; Protein-Serine-Threonine Kinases/metabolism; Proteolysis; RNA Interference; Toll-Like Receptors/agonists; Toll-Like Receptors/metabolism; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/genetics; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism; Ubiquitination |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0032688: negative regulation of interferon-beta production |
ECO:0000314: |
P |
Figure 1.E and 1.F, TRIP expression decreased overall amount of interferon being made when compared to control. |
complete | ||||
| GO:0032688: negative regulation of interferon-beta production |
ECO:0000314: |
P |
Figure 1.E TRIP expression decreased overall amount of interferon being made when compared to control thus indicating that TRAF interacting protein negatively regulates interferon-beta production. |
complete | ||||
|
involved_in |
GO:0032688: negative regulation of interferon-beta production |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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