The proteins belonging to the nuclear factor of activated T cells (NFAT) family 
of transcription factors are expressed in several cell types and regulate genes 
involved in differentiation, cell cycle and apoptosis. NFAT proteins share two 
conserved domains, the NFAT-homology region (NHR) and a DNA-binding domain 
(DBD). The N- and C-termini display two transactivation domains (TAD-N and 
TAD-C) that have low sequence similarity. Due to the high sequence conservation 
in the NHR and DBD, NFAT members have some overlapping roles in gene regulation. 
However, several studies have shown distinct roles for NFAT proteins in the 
regulation of cell death. The TAD-C shows low sequence similarity among NFAT 
family members, but its contribution to specific NFAT1-induced phenotypes is 
poorly understood. Here, we described at least two regions of NFAT1 TAD-C that 
confer pro-apoptotic activity to NFAT1. These regions extend from amino acids 
699 to 734 and 819 to 850 of NFAT1. We also showed that the NFAT1 TAD-C is 
unable to induce apoptosis by itself and requires a functional DBD. Furthermore, 
we showed that when fused to NFAT1 TAD-C, NFAT2, which is associated with cell 
transformation, induces apoptosis in fibroblasts. Together, these results 
suggest that the NFAT1 TAD-C includes NFAT death domains that confer to 
different NFAT members the ability to induce apoptosis.