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S ‐glutathionylation of IRF3 regulates IRF3–CBP interaction and activation of the IFNβ pathway
Author(s) -
Prinarakis Efthimios,
Chantzoura Eleni,
Thanos Dimitris,
Spyrou Giannis
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.28
Subject(s) - library science , foundation (evidence) , research center , basic research , biology , political science , computer science , law
Interferon regulatory factor 3 (IRF3) is an essential transcriptional regulator of the interferon genes. IRF3 is constitutively present in a latent conformation in the cell cytoplasm. In cells infected by Sendai virus, IRF3 becomes phosphorylated, homodimerizes, translocates to the nucleus, binds to target genes and activates transcription by interacting with CBP/p300 co‐activators. In this study, we report that in non‐infected cells IRF3 is post‐translationally modified by S ‐glutathionylation. Upon viral‐infection, it undergoes a deglutathionylation step that is controlled by the cytoplasmic enzyme glutaredoxin‐1 (GRX‐1). In virus‐infected GRX‐1 knockdown cells, phosphorylation, homodimerization and nuclear translocation of IRF3 were not affected, but the transcriptional activity of IRF3 and the expression of interferon‐β (IFNβ), were severely reduced. We show that deglutathionylation of IRF3 is necessary for efficient interaction of IRF3 with CBP, an event essential for transcriptional activation of the interferon genes. Taken together, these findings reveal a crucial role for S ‐glutathionylation and GRX‐1 in controlling the activation of IRF3 and IFNβ gene expression.