Identification and characterization of a novel nuclear factor of activatedT-cells-1 isoform expressed in mouse brain

The nuclear factor of activated T-cells (NFAT) family transcription factors play a key role in the control of cytokine gene expression in T-cells. Alt hough initially identified in T-cells, recent data have unveiled unanticipa ted roles for NFATs in the development, proliferation, and differentiation of other tissues. Here we report the identification, cDNA cloning, and func tional characterization of a new isoform of NFAT1 highly expressed in mouse brain. This isoform, which we named NPAT1-D, is identical to NFAT1 through out the N-terminal regulatory domain and the portion of the Rel domain whic h includes the minimal region required for specific binding to DNA and inte raction with AP-1. The homology stops sharply upstream of the 3'-boundary o f the Rel homology domain and is followed by a short unique C-terminal regi on. NFAT1-D was expressed at high levels in all brain districts and was fou nd as a constitutively active transcription complex. Transfection of a NFAT /luciferase reporter in the neuronal cell line PC12, which also expresses N FAT1-D, showed that these cells expressed a constitutive NFAT activity that was enhanced after nerve growth factor-induced differentiation but was res istant to the immunosuppressant cyclosporin A. NFAT1-D was, however, induci bly activated in a cyclosporin A-sensitive manner when expressed in T-cells , suggesting that the activity of NFAT proteins might be controlled by thei r specific cellular context.