Genes & Development · 2003 · 314 citations · 21 references
Life SciencesImmunologyMolecular BiologyCell SignalingGene ExpressionSignal TransductionAntiviral ImmunityCytokine BiologyInnate Immune ActivationInnate Immune ResponseInnate Immune Signaling PathwaysInterferon ResponsesAntiviral Innate Immune SignalingAntiviral Innate SignalingGene Activation MechanismsInterferon Signaling ResponsesInterferon-stimulated GenesJak-stat Signaling PathwayProtein Tyrosine PhosphorylationType I Interferon Pathways
ISG15 is one of the most strongly induced genes upon viral infection, type I interferon (IFN) stimulation, and lipopolysaccharide (LPS) stimulation. Here we report that mice lacking UBP43, a protease that removes ISG15 from ISGylated proteins, are hypersensitive to type I IFN. Most importantly, in UBP43-deficient cells, IFN-beta induces a prolonged Stat1 tyrosine phosphorylation, DNA binding, and IFN-mediated gene activation. Furthermore, restoration of ISG15 conjugation in protein ISGylation-defective K562 cells increases IFN-stimulated promoter activity. These findings identify UBP43 as a novel negative regulator of IFN signaling and suggest the involvement of protein ISGylation in the regulation of the JAK-STAT pathway.
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Inducible Gene Targeting in Mice
Ralf Kühn, Frieder Schwenk, Michel Aguet et al. · Science · 1995 · 1.9K citations · Full text