Transcriptional activation of the interleukin-6 gene by HTLV-1 p40tax through an NF-kappa B-like binding site.
The interleukin-6 (IL-6) gene is expressed by various stimuli including cytokines or viral infections, such as human T-cell leukemia virus type I (HTLV-1). However, it has not been well established how HTLV-1 induces the expression of the IL-6 gene. In the present study, we demonstrated that HTLV-1-derived transactivator protein, p40tax, could stimulate endogenous IL-6 gene expression. Furthermore, we showed that the NF-kappa B binding site (IL-6 kappa B site) located between -74 and -62 upstream of the cap site of the IL-6 gene was an essential cis-acting element for p40tax-mediated transactivation of the IL-6 gene expression by utilizing a series of 5' deletion mutants of the IL-6 5' flanking region as well as a construct with a mutated IL-6 kappa B site. We identified the presence of two nuclear factor complexes that bound to the IL-6 kappa B site. One was constitutively expressed, and the other was inducible by p40tax. Taken together, HTLV-1 p40tax directly induces IL-6 gene expression through the IL-6 kappa B site, indicating the close association between IL-6 overproduction and HTLV-1 infection.
Muraoka
O
O
Division of Molecular Oncology, Osaka University Medical School, Japan.
Kaisho
T
T
Tanabe
M
M
Hirano
T
T
D001483:Base Sequence; D001665:Binding Sites / Q000276:immunology; D015152:Blotting, Northern; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression / Q000276:immunology; D016356:Gene Products, tax / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000276:immunology*; D010957:Plasmids; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D016356:Gene Products, tax; D015850:Interleukin-6; D016328:NF-kappa B