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Central role of interferon regulatory factor-1 (IRF-1) in controlling retinoic acid inducible gene-I (RIG-I) expression.
- Source :
-
Journal of Cellular Physiology . Nov2007, Vol. 213 Issue 2, p502-510. 9p. 2 Black and White Photographs, 5 Graphs. - Publication Year :
- 2007
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Abstract
- Retinoic acid inducible gene-I (RIG-I) functions as the first line of defense against viral infection by sensing dsRNA and inducing type I interferon (IFN) production. The expression of RIG-I itself is induced by IFN-α/β and dsRNA. To comprehend the molecular mechanism of expression regulation, we cloned the RIG-I promoter and analyzed its activity upon IFN-β and dsRNA treatment. Under basal condition, RIG-I mRNA level and promoter activity were significantly higher in normal cells versus their tumor counterparts. In both normal and cancer cells, RIG-I expression was induced by IFN-β and dsRNA. A single IRF-1 binding site in the proximal promoter functioned as a crucial regulator of basal, IFN-β- and dsRNA-mediated induction of the RIG-I promoter. IFN-β and dsRNA treatment increased IRF-1 binding to the RIG-I promoter. IRF-1 expression was also higher in normal cells than in cancer cells and it was induced by IFN-β with similar kinetics as RIG-I. These results confirm that by controlling RIG-I expression, IRF-1 plays an essential role in anti-viral immunity. IRF-1 is a tumor suppressor and the expression profile of RIG-I together with its regulation by IRF-1 and the presence of a caspase-recruitment domain in RIG-I suggest that RIG-I might also possess tumor suppressor properties. J. Cell. Physiol. 213: 502–510, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219541
- Volume :
- 213
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Cellular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 26433133
- Full Text :
- https://doi.org/10.1002/jcp.21128