Protein ISGylation modulates the JAK-STAT signaling pathway

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 U...

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Veröffentlicht in:Genes & development 2003-02, Vol.17 (4), p.455-460
Hauptverfasser: Malakhova, Oxana A, Yan, Ming, Malakhov, Michael P, Yuan, Youzhong, Ritchie, Kenneth J, Kim, Keun Il, Peterson, Luke F, Shuai, Ke, Zhang, Dong-Er
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Sprache:eng
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Zusammenfassung: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.1056303