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Tumor necrosis factor alpha induces the adenovirus early 3 promoter by activation of NF-kappaB.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 1996 Nov 22; Vol. 271 (47), pp. 30249-55. - Publication Year :
- 1996
-
Abstract
- The early transcription unit 3 (E3) of human adenoviruses encodes proteins which appear to subvert host defense mechanisms. For example, the E3/19K protein inhibits the transport of major histocompatibility complex (MHC) class I molecules to the cell surface and thereby prevents cell lysis by cytotoxic T cells. Tumor necrosis factor alpha (TNF) stimulates expression of MHC molecules on the cell surface of normal cells but not of E3(+) cells, rather, a further reduction of MHC expression is evident. This was attributed to the increased expression of E3/19K upon TNF treatment, an effect also observed for other E3 proteins. We investigated the mechanism of the TNF-mediated up-regulation of E3 products. We show that TNF stimulates expression of a luciferase reporter gene driven by the E3 promoter. Mutation of individual transcription factor binding sites within the E3 promoter reveals the importance of the NF-kappaB binding site kappa2 for TNF inducibility. Electrophoretic mobility shift assays using antibodies directed against various members of the NF-kappaB family demonstrate that stimulation by TNF is mediated by the p50-p65 NF-kappaB complex. TNF inducibility does not depend on coexpression of E1A and can be observed during infection. Interestingly, the E3 promoter seems to be the only early promoter responsive to TNF and the only adenovirus promoter containing an NF-kappaB site. The implications of this regulatory mechanism for the adenovirus life cycle and its pathogenesis are discussed.
- Subjects :
- Adenovirus E1A Proteins genetics
Adenovirus E2 Proteins genetics
Cell Line
Fibroblasts drug effects
Fibroblasts metabolism
HeLa Cells
Humans
Mutagenesis, Site-Directed
Protein Binding
Transfection
Up-Regulation
Adenoviridae genetics
Gene Expression Regulation drug effects
NF-kappa B metabolism
Promoter Regions, Genetic
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 271
- Issue :
- 47
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 8939978
- Full Text :
- https://doi.org/10.1074/jbc.271.47.30249