Title: RNF220 mediates K63-linked polyubiquitination of STAT1 and promotes host defense.
Author:Guo X, Ma P, Li Y, Yang Y, Wang C, Xu T, Wang H, Li C, Mao B, Qi X.
Publication Name:Cell Death Differ
Pub Year: 2020
Doi:10.1038/s41418-020-00609-7
IF:10.717
Abstract:
STAT1is a master regulator that orchestrates type 1 and 2 interferon (IFN)-induced IFN-stimulated gene (ISG) expression. The mechanisms by whichSTAT1is phosphorylated and activated upon IFN signaling remain elusive. Our work demonstrated that ubiquitinationofSTAT1mediated by the E3 ligaseRNF220contributed significantly toSTAT1activation and innate immune responses.Rnf220gene deficiency resulted in the downregulationofIFN signaling and decreased expressionofISGs in response to type 1 and 2 IFNs stimulation andAcinetobacter baumanniiand HSV-1 infection. Mechanistically,RNF220interacted withSTAT1and mediated theK63-linkedpolyubiquitinationofSTAT1at residue K110, which promoted the interaction betweenSTAT1and the kinase JAK1. The expressionofRNF220was induced by pathogenic infection and IFN signaling.RNF220promotedSTAT1ubiquitination and phosphorylation through a positive feedback loop.RNF220haploinsufficiency impaired IFN signaling, andRNF220-defective mice were more susceptible toA. baumanniiand HSV-1 infection than WT mice. Our work offers novel insights into the mechanismsofSTAT1modulation and provides potential therapeutic targets against bacterial and viral infection and inflammatory diseases.
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