Requirements for interleukin 2 promoter transactivation by the Tax protein of human T-cell leukemia virus type 1.
The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) upregulates the expression of several cellular genes by activating members of both the NF-kappaB and bZIP families of transcription factors. Recent studies demonstrate that the CD28 response element (CD28RE) of the interleukin 2 (IL-2) promoter is the site upregulated by Tax in stimulated T cells. Although some reports suggest that this site is transactivated by NF-kappaB family members, others disagree, leaving the identity of the transcription factor(s) binding the CD28RE unclear. The studies presented here further characterize the response of the IL-2 promoter and CD28RE to the HTLV-1 Tax protein and demonstrate that the TATA-proximal AP-1 binding site of the IL-2 promoter is also necessary for Tax transactivation in stimulated Jurkat cells. In contrast to its upregulation of the IL-2 promoter which requires T-cell stimulation, Tax transactivates the isolated CD28RE-AP-1 element without stimulation but is greatly synergized by calcium ionophore and phorbol ester. Additionally, transactivation of the IL-2 promoter requires the Tax activation domain involved in upregulation of bZIP-enhanced transcription while the NF-kappaB-activating domain of Tax is dispensable. Interestingly, both domains appear to be necessary for the activation of the isolated CD28RE-AP-1 sequence in the context of a heterologous promoter construct. This strongly suggests that activation of NF-kappaB is insufficient to activate transcription via the CD28RE-AP-1 element of the IL-2 promoter and that a different transcription factor, upregulated via the activation domain of the HTLV-1 Tax protein, may be involved.
Curtiss
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VE
Department of Biology, San Diego State University, California 92182-4614, USA.
Smilde
R
R
McGuire
K L
KL
D001483:Base Sequence; D001665:Binding Sites; D018106:CD28 Antigens / Q000378:metabolism; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D013006:Growth Hormone / Q000096:biosynthesis; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics*; D015759:Ionomycin / Q000494:pharmacology; D008156:Luciferases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D018106:CD28 Antigens; D016356:Gene Products, tax; D007376:Interleukin-2; D016328:NF-kappa B; D011994:Recombinant Proteins; D014157:Transcription Factors; D015759:Ionomycin; D013006:Growth Hormone; D008156:Luciferases; D013755:Tetradecanoylphorbol Acetate