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) upregul ates the expression of several cellular genes by activating members of both the NF-kappa B and bZIP families of transcription factors. Recen t studies demonstrate that the CD28 response element (CD28RE) of the i nterleukin 2 (IL-2) promoter is the site upregulated by Tax in stimula ted T cells. Although some reports suggest that this site is transacti vated by NF-kappa B family members, others disagree, leaving the ident ity of the transcription factor(s) binding the CD28RE unclear. The stu dies presented here further characterize the response of the IL-2 prom oter and CD28RE to the HTLV-1 Tax protein and demonstrate that the TAT A-proximal AP-1 binding site of the IL-2 promoter is also necessary fo r Tax transactivation in stimulated Jurkat cells. In contrast to its u pregulation of the IL-2 promoter which requires T-cell stimulation, Ta x transactivates the isolated CD28RE-AP-1 element without stimulation but is greatly synergized by calcium ionophore and phorbol ester. Addi tionally, transactivation of the IL-2 promoter requires the Tax activa tion domain involved in upregulation of bZIP-enhanced transcription wh ile the NF-KB-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 constr uct. This strongly suggests that activation of NF-kappa B is insuffici ent to activate transcription via the CDZ8RE-AP-1 element of the IL-2 promoter and that a different transcription factor, upregulated via th e activation domain of the HTLV-1 Tax protein, may be involved.