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

• Autoři: WILLEMSEN Joschka; WICHT Oliver; WOLANSKI Julia; BAUR Nina; BASTIAN Sandra; HAAS Darya; MATULA Petr; KNAPP Bettina; MEYNIEL-SCHICKLIN Laurene; WANG Chen; BARTENSCHLAGER Ralf; LOHMANN Volker; ROHR Karl; ERFLE Holger; KADERALI Lars; MARCOTRIGIANO Joseph; PICHLMAIR Andreas; BINDER Marco
• Rok publikování: 2017
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: Molecular Cell
• Fakulta / Pracoviště MU: Fakulta informatiky
• www: http://dx.doi.org/10.1016/j.molcel.2016.12.021
• Doi: http://dx.doi.org/10.1016/j.molcel.2016.12.021
• Klíčová slova: innate immunity; antiviral response; pattern recognition receptors; signal transduction; feedback regulation; interferon system; cytokines; DAPK1; RIG-I; DDX58
• Popis: 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.

Související projekty

• Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii