Abstract
Tumor necrosis factor receptor-related 2 (TR2, HVEM or TNFRSF-14) plays an important role in immune responses, however, the mechanisms regulating its expression are unclear. To understand the control of TR2 gene expression, we studied the upstream region of the gene. Gel supershift assays revealed inducible binding of nuclear factor of activated T cells (NFAT) to a putative NFAT site within the TR2 promoter. Furthermore, cotransfection of a dominant negative NFAT construct, or siRNA for NFAT, resulted in increased expression of a TR2 reporter gene. Our findings demonstrate that NFAT negatively regulates TR2 expression in activated T cells.
Highlights
Members of the tumor necrosis factor receptor (TNFR) family interact with a set of ligands forming the TNF family
The nuclear translocation of nuclear factor of activated T cells (NFAT) proteins is controlled by calcineurin (CaN), a Ca2+-dependent phophatase, and CaN is highly sensitive to cyclosporine A (CsA) (Shaw et al, 1995), which prevents CaN-dependent nuclear translocation of NFAT
Of the NFAT family members, NFATc1 and NFATc2 are expressed predominantly in lymphocytes, and NFATc3 is expressed in T cells (Rengarajan et al, 2002; Macian, 2005)
Summary
Members of the tumor necrosis factor receptor (TNFR) family interact with a set of ligands forming the TNF family. Tumor Necrosis Factor Receptor Related 2 (TR2, HVEM or TNFRSF-14) is expressed in various tissues and immune cells, including T cells, B cells and dendritic cells (DC). Members of the nuclear factor of activated T cells (NFAT) family are widely expressed in cells of the immune system, including T cells. They are involved in T cell regulation (Rengarajan et al, 2002), and the expression of many inducible genes, including cytokines such as IL-4, and IFN-γ (Yoshida et al, 1998) and TNF family members such as TNF-α, and LIGHT (Macian, 2005). The nuclear translocation of NFAT proteins is controlled by calcineurin (CaN), a Ca2+-dependent phophatase, and CaN is highly sensitive to cyclosporine A (CsA) (Shaw et al, 1995), which prevents CaN-dependent nuclear translocation of NFAT
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