Phosphorylation-Dependent Feedback Inhibition of RIG-I by DAPK1 Identified by Kinome-wide siRNA Screening
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28132841
DOI
10.1016/j.molcel.2016.12.021
PII: S1097-2765(16)30864-4
Knihovny.cz E-zdroje
- Klíčová slova
- DAPK1, DDX58, RIG-I, antiviral response, cytokines, feedback regulation, innate immunity, interferon system, pattern recognition receptors, signal transduction,
- MeSH
- buňky A549 MeSH
- fosforylace MeSH
- HEK293 buňky MeSH
- kultivované buňky MeSH
- lidé MeSH
- malá interferující RNA genetika MeSH
- myši MeSH
- proteinkinasy asociované se smrtí metabolismus MeSH
- proteinkinasy metabolismus MeSH
- receptory kyseliny retinové metabolismus MeSH
- signální transdukce MeSH
- zpětná vazba fyziologická MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DAPK1 protein, human MeSH Prohlížeč
- malá interferující RNA MeSH
- PLAAT4 protein, human MeSH Prohlížeč
- proteinkinasy asociované se smrtí MeSH
- proteinkinasy MeSH
- receptory kyseliny retinové MeSH
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.
Citace poskytuje Crossref.org
