CONSTITUTIVE DEPHOSPHORYLATION AND ACTIVATION OF A MEMBER OF THE NUCLEAR FACTOR OF ACTIVATED T-CELLS, NF-AT1, IN TAX-EXPRESSING AND TYPE-I HUMAN T-CELL LEUKEMIA VIRUS-INFECTED HUMAN T-CELLS

The tax gene product of the type I human T-cell leukemia virus (HTLV-I ) transactivates interleukin-2 (IL-2) gene through activation of an en hancer termed CD28 responsive element (CD28RE). Tax activation of the CD28RE is partially mediated by a member of the nuclear factor of acti vated T cells, NF-AT1. We have previously shown that NF-AT1 is constit utively active in Jurkat T cells stably transfected with the Tax cDNA, although the underlying molecular mechanism and physiological relevan ce of this finding remain unclear. In this report, we demonstrate that the active form of NF-AT1 is also present in the nuclei of HTLV-I-tra nsformed T cells that express the Tax protein. Interestingly, the cons titutive activation of NF-AT1 in these T cells is associated with its dephosphorylation. Furthermore, the dephosphorylated NF-AT1 can be rap idly re-phosphorylated when the cells are incubated with cyclosporin A , an immunosuppressant inhibiting the serine/threonine phosphatase cal cineurin. These results suggest that activation of NF-AT1 in Tax-expre ssing and HTLV-I-transformed T cells results from its dephosphorylatio n, which in turn may be due to deregulation of calcineurin.