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

Joschka Willemsen, Oliver Wicht, Julia C. Wolanski, Nina Baur, Sandra Bastian, Darya A. Haas, Petr Matula, Bettina Knapp, Laurène Meyniel-Schicklin, Chen Wang, Ralf Bartenschlager, Volker Lohmann, Karl Rohr, Holger Erfle, Lars Kaderali, Joseph Marcotrigiano, Andreas Pichlmair, Marco Binder

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageEnglish
Pages (from-to)403-415.e8
JournalMolecular Cell
Issue number3
StatePublished - 2 Feb 2017
Externally publishedYes


  • DAPK1
  • DDX58
  • RIG-I
  • antiviral response
  • cytokines
  • feedback regulation
  • innate immunity
  • interferon system
  • pattern recognition receptors
  • signal transduction


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