Regulation of HTLV-I gene expression by tax and AP-2

The HTLV-I transactivator protein tax activates expression of both viral and cellular genes. In addition it has been demonstrated to repress expression of the DNA beta-polymerase gene. We wished to investigate potential interactions between tax and the cellular transcription factor AP-2 which binds to distinct motifs in each of the three 21-bp repeat sequences in the HTLV-I LTR. First we demonstrate that AP-2 is capable of activating HTLV-I gene expression. Cotransfection experiments reveal that AP-2 and tax are capable of inhibiting each other's ability to activate HTLV-I gene expression. The mechanism of this inhibition was studied by gel retardation analysis using both bacterial and in vitro synthesized AP-2 and tax proteins. These results indicate that tax inhibits the ability of AP-2 to bind to the 21-bp repeat. Mutational analysis of both tax and AP-2 demonstrate that the amino termini of both proteins are potential sites of interaction. These results are consistent with a model in which AP-2 and tax can potentially form protein complexes resulting in an altered ability of each factor to modulate HTLV-I gene expression.