A novel c-Jun-dependent signal transduction pathway necessary for the transcriptional activation of interferon gamma response genes.
J Biol Chem
; 282(2): 938-46, 2007 Jan 12.
Article
en En
| MEDLINE
| ID: mdl-17105733
ABSTRACT
The biological effects of interferon gamma (IFNgamma) 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 IFNgamma rapidly activated AP-1 DNA binding that required c-Jun but was independent of JAK1 and STAT1. IFNgamma-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 IFNgamma-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 IFNgamma. Thus, IFNgamma 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 IFNgamma that proceeds in parallel with conventional JAK/STAT signaling to activate ISGs.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Activación Transcripcional
/
Interferón gamma
/
Proteínas Proto-Oncogénicas c-jun
/
Sistema de Señalización de MAP Quinasas
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2007
Tipo del documento:
Article
País de afiliación:
Australia