Influence of human T-cell leukemia virus type I tax and rex on interleukin-2 gene expression.
The X region of human T-cell leukemia virus type I (HTLV-I) encodes two proteins that regulate viral gene expression. The tax protein is the product of the transactivator gene and has been shown to up-regulate the expression of some cellular genes controlling T-cell replication, including that of the interleukin-2 (IL-2) T-cell growth hormone and the alpha chain of its receptor (IL-2R). Several studies have shown that tax transactivation of the IL-2R alpha-chain promoter is mediated by binding sites for the transcriptional activator NF-kappa B, and this mechanism has also been implicated in the tax activation of IL-2 promoter activity. The rex gene product of HTLV-I regulates viral protein production by influencing mRNA expression and has been implicated in the stabilization of IL-2R alpha-chain mRNA. In the present studies, the ability of the tax and rex proteins to transactivate IL-2 gene expression has been reinvestigated. The ability of the tax protein to transactivate IL-2 promoter activity appears, at least in part, to be mediated by the recognition sequence for a DNA-binding complex known as CD28RC. Consistent with this hypothesis is the observation that tax-mediated activation of IL-2 gene expression is resistant to the immunosuppressive affects of cyclosporin A, a property postulated for the CD28RC binding complex. Unexpectedly, this tax-mediated up-regulation of IL-2 expression is synergized by the presence of the rex protein. These findings demonstrate that transactivation of IL-2 gene expression by tax is augmented by mechanisms distinct from NF-kappa B and raise the possibility that rex, as well as tax, contributes to the oncogenic capability of HTLV-I by altering the expression of the IL-2 gene in T cells infected with this retrovirus.
McGuire
K L
KL
Department of Biology and Molecular Biology Institute, College of Sciences, San Diego State University, California 92182-0057.
Curtiss
V E
VE
Larson
E L
EL
Haseltine
W A
WA
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001483:Base Sequence; D018106:CD28 Antigens; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology; D004252:DNA Mutational Analysis; D004274:DNA, Recombinant / Q000235:genetics; D004268:DNA-Binding Proteins; D016355:Genes, pX / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000166:cytology; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D016572:Cyclosporine; D015500:Chloramphenicol O-Acetyltransferase