| Literature DB >> 28132841 |
Joschka Willemsen1, Oliver Wicht2, Julia C Wolanski3, Nina Baur2, Sandra Bastian3, Darya A Haas4, Petr Matula5, Bettina Knapp6, Laurène Meyniel-Schicklin7, Chen Wang8, Ralf Bartenschlager9, Volker Lohmann9, Karl Rohr10, Holger Erfle11, Lars Kaderali12, Joseph Marcotrigiano8, Andreas Pichlmair4, Marco Binder13.
Abstract
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.Entities:
Keywords: DAPK1; DDX58; RIG-I; antiviral response; cytokines; feedback regulation; innate immunity; interferon system; pattern recognition receptors; signal transduction
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Year: 2017 PMID： 28132841 DOI： 10.1016/j.molcel.2016.12.021
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970