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Journal Article

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

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons185890

Haas,  Darya A.
Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78510

Pichlmair,  Andreas
Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Willemsen, J., Wicht, O., Wolanski, J. C., Baur, N., Bastian, S., Haas, D. A., et al. (2017). Phosphorylation-Dependent Feedback Inhibition of RIG-I by DAPK1 Identified by Kinome-wide siRNA Screening. Molecular Cell, 65(3), 403-415. doi:10.1016/j.molcel.2016.12.021.


Cite as: http://hdl.handle.net/21.11116/0000-0001-6FE0-6
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.