A novel molecular mechanism of interferon alpha-regulated expression of retinoic acid-induced gene G.
- Author:
Ye-jiang LOU
1
;
Xiao-rong PAN
;
Pei-min JIA
;
Dong LI
;
Zhang-lin ZHANG
;
Gui-ping XU
;
Jian-hua TONG
Author Information
- Publication Type:Journal Article
- MeSH: Cell Line, Tumor; Fibrosarcoma; metabolism; pathology; Gene Expression Regulation, Neoplastic; Humans; Immunoprecipitation; Interferon-Stimulated Gene Factor 3, gamma Subunit; genetics; metabolism; Interferon-alpha; pharmacology; Intracellular Signaling Peptides and Proteins; genetics; metabolism; Leukemia, Promyelocytic, Acute; metabolism; pathology; Phosphorylation; Plasmids; STAT1 Transcription Factor; genetics; metabolism; STAT2 Transcription Factor; genetics; metabolism; Signal Transduction; Transfection
- From: Chinese Journal of Oncology 2010;32(2):88-92
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the molecular mechanisms by which IFN-alpha regulated retinoic acid-induced gene G (RIG-G) expression.
METHODSThe expression of STAT1, p-STAT1 and RIG-G in IFN-alpha-treated NB4 cells was detected by Western blot. The roles of STAT1, STAT2 and IRF-9 in IFN-alpha-induced RIG-G expression were analyzed in STAT1-null U3A cells by cell transfection, reporter gene assay, co-immunoprecipitation and chromatin immunoprecipitaion.
RESULTSIn U3A cells, only when STAT2 and IRF-9 were co-transfected, the luciferase activities of RIG-G promoter-containing reporter gene could be highly increased about 8-fold compared with that in the control group. Moreover, in the absence of IFN-alpha, similar effects were observed in either IRF-9 co-transfected with wild type or mutant form of STAT2, whereas IFN-alpha could increase the transactivation activity of wild type STAT2 and IRF-9 by 6-fold compared with that without IFN-alpha, but had no effect on mutant STAT2. In addition, STAT2 could interact with IRF-9 and bind to the RIG-G promoter.
CONCLUSIONSTAT2 may interact with IRF-9 in a STAT1-independent manner. The complex STAT2/IRF-9 is the key factor mediating the expression of RIG-G gene regulated by IFN-alpha. This is a novel signal transduction cascade for IFN which is different from the classical JAK-STAT pathway.
