FasL promoter activation by IL-2 through SP1 and NFAT but not Egr-2 and Egr-3

Recently activated peripheral T cells treated with IL-2 for 4 days expresse d Fas ligand (FasL)-mediated cytotoxicity. These IL-2-treated T cells had h igh nuclear expression of SP1 and NFAT, but lacked the Egr-2 and Egr-3 that could be induced by anti-CD3 stimulation and had been implicated in Fast g ene activation. A minimal promoter region that responded to IL-2 was identi fied by transient transfection assays using deletion mutants. The data sugg ests that the GGGCGGAAA site present in the 5' end of the minimal Fast prom oter is critical to IL-2-induced Fast gene activation. The GGGCGGAAA sequen ce contains an overlapping site used by two transcription factor families, one (GGGCGG) for the SP1 family and the other (GGAAA) for the NFAT family. Fast promoter activity was partially but statistically significantly reduce d with constructs mutated at either site. More activity was lost with a con struct mutated at both sites. In contrast, mutation at the Egr site had no effect on IL-2-induced Fast promoter activity. Our study identified a new F ast promoter site responding to IL-2-induced SP1 and NFAT factors. Furtherm ore, the nuclei of IL-2-treated cells express SP1 and NFAT, but not Egr-2 a nd Egr-3, for FasL gene activation.