| First Author | Willemsen J | Year | 2017 |
| Journal | Mol Cell | Volume | 65 |
| Issue | 3 | Pages | 403-415.e8 |
| PubMed ID | 28132841 | Mgi Jnum | J:253023 |
| Mgi Id | MGI:6094777 | Doi | 10.1016/j.molcel.2016.12.021 |
| Citation | Willemsen J, et al. (2017) Phosphorylation-Dependent Feedback Inhibition of RIG-I by DAPK1 Identified by Kinome-wide siRNA Screening. Mol Cell 65(3):403-415.e8 |
| abstractText | 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. |
