Back to Search
Start Over
Promoter Organization of the Interferon-A Genes Differentially Affects Virus-induced Expression and Responsiveness to TBK1 and IKK&3x20AC;.
- Source :
-
Journal of Biological Chemistry . 2/24/2006, Vol. 281 Issue 8, p4856-4866. 11p. 2 Charts, 5 Graphs. - Publication Year :
- 2006
-
Abstract
- Virus-induced expression of interferon (IFN)-A genes is regulated by two members of the IFN regulatory factor (IRF) family, IRF-3 and IRF-7, which are activated by phosphorylation during viral infection by the IKK-related serine/threonine kinases TBK1 and IκB kinase ϵ (IKKϵ). In this study, we demonstrate that three IRF-binding sites located in the virus-responsive element mediate the transcriptional activation of the IFN-A4 promoter by IRF-3. The precise arrangement of these IRF elements is required for synergistic activation of the IFN-A4 promoter following Newcastle disease virus infection or activation by TBK1 or IKKϵ. The ordered assembly of IRF-3 multimers on the promoter also determines cooperative recruitment of IRF-3 and CREB-binding protein and differential virus-induced expression of IFN-A4 gene promoter compared with IFN-A11. Naturally occurring nucleotide substitutions disrupt two of the IRF elements in the IFN-A11 gene promoter, leading to a dramatic decrease in IRF-3 and CREB-binding protein recruitment and in IRF-3-dependent transcription. Transcription of the IFN-A4 promoter by IRF-7 is mediated by two IRF elements; promoter mutants that carry a reversed IRF element retain the ability to respond to IKKϵ or TBK1 expression in the presence of IRF-7 but lose the capacity to respond to virus or kinase-induced IRF-3. Interestingly, IKKϵ or TBK1 stimulates the IRF-7-mediated transcription of IFN-A11, although at a lesser extent compared with IFN-A4. Our data indicate that virus-induced expression of IFN-A genes is dictated by the organization of IRF elements within the IFN-A promoters and that the differential IFN-A gene expression, based on the IRF-3 responsiveness, is partially compensated in the presence of IRF-7 when both factors are activated by IKKϵ or TBK1. [ABSTRACT FROM AUTHOR]
- Subjects :
- *VIRUSES
*INTERFERONS
*GENES
*PHOSPHORYLATION
*ANTIVIRAL agents
*VIRUS diseases
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 281
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20436340
- Full Text :
- https://doi.org/10.1074/jbc.M506812200