Schematic of NFAT interaction partners in naive T cells. T-cell activation requires TCR and costimulatory signals. NFAT is engaged via the TCR proximal signaling cascades and other signaling pathways, converges in the nucleus, and activates gene transcription. IL-2 via the IL-2R activates STAT5 and, subsequently, cell-cycle entry. Runx3 and Runx1 cooperate together with NF-κB with NFAT/AP-1 on the Il2 promoter to activate Il2, whereas the NFAT/Foxp3 complex suppresses Il2 transcription as well as the NFAT autoregulatory loop on the Nfat2 promoter. The expression of Il4 in naive cells is suppressed via the direct binding of Mina and NFAT to its promoter. In addition, NFAT/AP-1 activates the transcription of Cd25 (Il2Rα). NFAT functions as a negative regulator of GITR expression and is suppressed by PPARγ, p21SWIF, inducible cyclic adenosine monophosphate early repressor (ICER), and NR2F6.