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

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 unaffe..