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

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.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-6FE0-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-6FE1-5
Genre: Journal Article

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 Creators:
Willemsen, Joschka1, Author
Wicht, Oliver1, Author
Wolanski, Julia C.1, Author
Baur, Nina1, Author
Bastian, Sandra1, Author
Haas, Darya A.2, Author              
Matula, Petr1, Author
Knapp, Bettina1, Author
Meyniel-Schicklin, Laurene1, Author
Wang, Chen1, Author
Bartenschlager, Ralf1, Author
Lohmann, Volker1, Author
Rohr, Karl1, Author
Erfle, Holger1, Author
Kaderali, Lars1, Author
Marcotrigiano, Joseph1, Author
Pichlmair, Andreas2, Author              
Binder, Marco1, Author
Affiliations:
1external, ou_persistent22              
2Pichlmair, Andreas / Innate Immunity, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565166              

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Free keywords: INNATE IMMUNE RECEPTOR; PERSISTENT LCMV INFECTION; PROTEIN-KINASE; STRUCTURAL BASIS; BETA-CATENIN; MITOCHONDRIAL-MEMBRANE; INTERFERON SYSTEM; ISG15 CONJUGATION; RNA RECOGNITION; QUANTIFICATIONBiochemistry & Molecular Biology; Cell Biology;
 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.

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Language(s): eng - English
 Dates: 2017-01-262017
 Publication Status: Published in print
 Pages: 21
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
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Title: Molecular Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 65 (3) Sequence Number: - Start / End Page: 403 - 415 Identifier: ISSN: 1097-2765
CoNE: https://pure.mpg.de/cone/journals/resource/954925610929