NFATX, A NOVEL MEMBER OF THE NUCLEAR FACTOR OF ACTIVATED T-CELLS FAMILY THAT IS EXPRESSED PREDOMINANTLY IN THE THYMUS

The nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the prom oters of cytokine genes. Here, we report the cDNA cloning, chromosomal localization, and initial characterization of a transcription factor related to NFATp and NFATc. The novel molecule, designated NFATx, exhi bits in its middle a region very similar to the Rel homology domain in NFATc and NFATp. The amino-terminal region of NFATx also shows signif icant similarities to corresponding sequences in NFATc and NFATp and c ontains three copies of a conspicuous 17-residue motif of unknown func tion. We provide evidence showing that NFATx can reconstitute binding to the NFAT-binding site from the interleukin 2 promoter when combined with AP1 (c-Fos/c-Jun) polypeptides and that NFATx is capable of acti vating transcription of the interleukin 2 promoter in COS-7 cells when stimulated with phorbol ester and calcium ionophore. NFATx mRNA is pr eferentially and remarkably found in the thymus and at lower levels in peripheral blood leukocytes. The expression pattern of NFATx, togethe r with its functional activity, strongly suggests that NFATx plays a r ole in the regulation of gene expression in T cells and immature thymo cytes.