Molecular cell, 2017-02, Vol.65 (3), p.403-415.e8
2017
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- Autor(en) / Beteiligte
- Titel
- Phosphorylation-Dependent Feedback Inhibition of RIG-I by DAPK1 Identified by Kinome-wide siRNA Screening
- Ist Teil von
- Molecular cell, 2017-02, Vol.65 (3), p.403-415.e8
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. [Display omitted] •siRNA screen of antiviral RIG-I/IRF3 pathway (human kinome) was performed•DAPK1 was identified as a negative-feedback regulator of the RIG-I pathway•RIG-I-mediated antiviral signaling activates DAPK1 kinase activity•DAPK1 inactivates RIG-I RNA sensing by direct phosphorylation of RIG-I Willemsen et al. screened the antiviral RIG-I pathway for regulators and identified and validated 22 kinases. They describe an inhibitory feedback loop mediated by DAPK1. Antiviral signaling activates DAPK1 kinase activity, which, in turn, inactivates RIG-I by direct phosphorylation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-2765eISSN: 1097-4164DOI: 10.1016/j.molcel.2016.12.021Titel-ID: cdi_proquest_miscellaneous_1862939861
- Format
- –
- Schlagworte
- A549 Cells, Animals, antiviral response, Cells, Cultured, cytokines, DAPK1, DDX58, Death-Associated Protein Kinases - metabolism, feedback regulation, Feedback, Physiological, HEK293 Cells, Humans, innate immunity, interferon system, Mice, pattern recognition receptors, Phosphorylation, Protein Kinases - metabolism, Receptors, Retinoic Acid - metabolism, RIG-I, RNA, Small Interfering - genetics, Signal Transduction