Publication details

Phosphorylation-Dependent Feedback Inhibition of RIG-I by DAPK1 Identified by Kinome-wide siRNA Screening

Authors

WILLEMSEN Joschka WICHT Oliver WOLANSKI Julia BAUR Nina BASTIAN Sandra HAAS Darya MATULA Petr KNAPP Bettina MEYNIEL-SCHICKLIN Laurene WANG Chen BARTENSCHLAGER Ralf LOHMANN Volker ROHR Karl ERFLE Holger KADERALI Lars MARCOTRIGIANO Joseph PICHLMAIR Andreas BINDER Marco

Type Article in Periodical
Magazine / Source Molecular Cell
MU Faculty or unit

Faculty of Informatics

Citation
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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