PMID: 23478265 RLIMS-P 5 Check other iTextMine results Issue Report
Title
| 1. | Human DEAD box helicase 3 couples IκB kinase ε to interferon regulatory factor 3 activation. |
Abstract
| 2. | The human DEAD box protein 3 (DDX3) has been implicated in different processes contributing to gene expression. |
| 3. | Interestingly, DDX3 is required as an essential host factor for the replication of HIV and hepatitis C virus (HCV) and is therefore considered a potential drug target. |
| 4. | On the other hand, DDX3 interacts with IκB kinase ε (IKKε) and TANK-binding kinase 1 (TBK1) and contributes to the induction of antiviral type I interferons (IFNs). |
| 5. | However, the molecular mechanism by which DDX3 contributes to IFN induction remains unclear. |
| 6. | Here we show that DDX3 mediates phosphorylation of interferon regulatory factor 3 (IRF3) by the kinase IKKε. |
| 7. | DDX3 directly interacts with IKKε and enhances its autophosphorylation and activation. |
| 8. | IKKε then phosphorylates several serine residues in the N terminus of DDX3. |
| 9. | Phosphorylation of DDX3 at serine 102 (S102) is required for recruitment of IRF3 to DDX3, facilitating its phosphorylation by IKKε. |
| 10. | Mutation of S102 to alanine disrupted the interaction between DDX3 and IRF3 but not that between DDX3 and IKKε. |
| 11. | The S102A mutation failed to enhance ifnb promoter activation, suggesting that the DDX3-IRF3 interaction is crucial for this effect. |
| 12. | Our data implicates DDX3 as a scaffolding adaptor that directly facilitates phosphorylation of IRF3 by IKKε. |
| 13. | DDX3 might thus be involved in pathway-specific activation of IRF3. |
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