Polo-like Kinase 1 (PLK1) Regulates Interferon (IFN) Induction by MAVS

摘要: The mitochondria-bound adapter MAVS participates in IFN induction by recruitment of downstream partners such as members the TRAF family, leading to activation NF-κB, and IRF3 pathways. A yeast two-hybrid search for MAVS-interacting proteins yielded Polo-box domain (PBD) mitotic Polo-like kinase PLK1. We showed that PBD associates with two different domains both dependent independent phosphorylation events. phosphodependent association requires phosphopeptide binding ability PBD. It takes place proline-rich MAVS, within an STP motif, characteristic PLK1 its targets, where central Thr234 residue is phosphorylated. Its phosphoindependent at C terminus MAVS. strongly inhibits activate NF-κB pathways induce IFN. Reciprocally, depletion can increase response RIG-I/SeV or RIG-I/poly(I)-poly(C) treatments. This inhibition on it disrupts partner TRAF3. was inhibited cells arrested G2/M nocodazole, which provokes increased expression endogenous Interestingly, from these nocodazole-treated could restore, least partially, induction. Altogether, data demonstrate a new function regulator provide basis development inhibitors preventing PLK1/MAVS sustain innate immunity.