Phosphorylation-Dependent Feedback Inhibition of RIG-I by DAPK1 Identified by Kinome-wide siRNA Screening
| Authors | |
|---|---|
| Year of publication | 2017 |
| Type | Article in Periodical |
| Magazine / Source | Molecular Cell |
| MU Faculty or unit | |
| Citation | |
| Web | http://dx.doi.org/10.1016/j.molcel.2016.12.021 |
| Doi | http://dx.doi.org/10.1016/j.molcel.2016.12.021 |
| Keywords | innate immunity; antiviral response; pattern recognition receptors; signal transduction; feedback regulation; interferon system; cytokines; DAPK1; RIG-I; DDX58 |
| Description | Cell-autonomous induction of type I interferon must be stringently regulated. Rapid induction is key to control virus infection, whereas proper limitation of signaling is essential to prevent immunopathology and autoimmune disease. Using unbiased kinome-wide RNAi screening followed by thorough validation, we identified 22 factors that regulate RIG-I/IRF3 signaling activity. We describe a negative-feedback mechanism targeting RIG-I activity, which is mediated by death associated protein kinase 1 (DAPK1). RIG-I signaling triggers DAPK1 kinase activation, and active DAPK1 potently inhibits RIG-I stimulated IRF3 activity and interferon-beta production. DAPK1 phosphorylates RIG-I in vitro at previously reported as well as other sites that limit 5'ppp-dsRNA sensing and virtually abrogate RIG-I activation. |
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