A novel c-Jun-dependent signal transduction pathway necessary for the transcriptional activation of interferon γ response genes

Daniel J. Gough, Kanaga Sabapathy, Enoch Yi No Ko, Helen A. Arthur, Robert D. Schreiber, Joseph A. Trapani, Christopher J.P. Clarke, Ricky W. Johnstone

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

The biological effects of interferon γ (IFNγ) are mediated by interferon-stimulated genes (ISGs), many of which are activated downstream of Janus kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) signaling. Herein we have shown that IFNγ rapidly activated AP-1 DNA binding that required c-Jun but was independent of JAK1 and STAT1. IFNγ-induced c-Jun phosphorylation and AP-1 DNA binding required the MEK1/2 and ERK1/2 signaling pathways, whereas the JNK1/2 and p38 mitogen-activated protein kinase pathways were dispensable. The induction of several ISGs, including ifi-205 and iNOS, was impaired in IFNγ-treated c-Jun-/- cells, but others, such as IP-10 and SOCS3, were unaffected, and chromatin immunoprecipitation demonstrated that c-Jun binds to the iNOS promoter following treatment with IFNγ. Thus, IFNγ induced JAK1- and STAT1-independent activation of the ERK mitogen-activated protein kinase pathway, phosphorylation of c-Jun, and activation of AP-1 DNA binding, which are important for the induction of a subset of ISGs. This represents a novel signal transduction pathway induced by IFNγ that proceeds in parallel with conventional JAK/STAT signaling to activate ISGs.

Original languageEnglish
Pages (from-to)938-946
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number2
DOIs
StatePublished - Jan 12 2007

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