Phosphorylation-Dependent Feedback Inhibition of RIG-I by DAPK1 Identified by Kinome-wide siRNA Screening
Copyright © 2017 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:65 |
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| Enthalten in: |
Molecular cell - 65(2017), 3 vom: 02. Feb., Seite 403-415.e8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Willemsen, Joschka [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.09.2017 Date Revised 28.08.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.molcel.2016.12.021 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Phosphorylation-Dependent Feedback Inhibition of RIG-I by DAPK1 Identified by Kinome-wide siRNA Screening |
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| 520 | |a Copyright © 2017 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Wicht, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Wolanski, Julia C |e verfasserin |4 aut | |
| 700 | 1 | |a Baur, Nina |e verfasserin |4 aut | |
| 700 | 1 | |a Bastian, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Haas, Darya A |e verfasserin |4 aut | |
| 700 | 1 | |a Matula, Petr |e verfasserin |4 aut | |
| 700 | 1 | |a Knapp, Bettina |e verfasserin |4 aut | |
| 700 | 1 | |a Meyniel-Schicklin, Laurène |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Bartenschlager, Ralf |e verfasserin |4 aut | |
| 700 | 1 | |a Lohmann, Volker |e verfasserin |4 aut | |
| 700 | 1 | |a Rohr, Karl |e verfasserin |4 aut | |
| 700 | 1 | |a Erfle, Holger |e verfasserin |4 aut | |
| 700 | 1 | |a Kaderali, Lars |e verfasserin |4 aut | |
| 700 | 1 | |a Marcotrigiano, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Pichlmair, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Binder, Marco |e verfasserin |4 aut | |
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