The gene expression of murine TR-2/HVEM is regulated by NFAT

TR2 (TNFR-related 2 or HVEM) is a member of the TNFR family with homology to TNFRII. To understand the mechanisms regulating the expression of TR2 in T cells, we cloned and analyzed the 5' flanking region of mTR2 (murine TR2). We identified the NFAT and AP-1 binding sites by site directed mutagenesis of the mTR2 promoter; mutation of these sites increased TR2 expression. TR2 promoter activity was increased significantly by cyclosporine. A treatment and the involvement of NFATc4 in TR2 promoter regulation was confirmed by electrophoretic mobility supershift analysis. Together, these results suggest that NFATc4 and AP-1 are negative regulators of its expression.