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Brief Definitive Reports |
Chain/CD25 Promoter Is a Target for Nuclear Factor of Activated T Cells
Institute of Virology and Immunobiology, University of Würzburg, D-97080 Würzburg, Germany
The expression of the murine interleukin (IL)-2 receptor
chain/CD25 is strongly induced at the transcriptional level after T cell activation. We show here that nuclear factor of activated T cell (NF-AT) factors are involved in the control of CD25 promoter induction in T cells. NF-ATp and NF-ATc bind to two sites around positions –585 and –650 located upstream of the proximal CD25 promoter. Immediately 3' from these NF-AT motifs, nonconsensus sites are located for the binding of AP-1–like factors. Mutations of sites that suppress NF-AT binding impair the induction and strong NF-ATp–mediated transactivation of the CD25 promoter in T cells. In T lymphocytes from NF-ATp–deficient mice, the expression of CD25 is severely impaired, leading to a delayed IL-2 receptor expression after T cell receptor (TCR)/CD3 stimulation. Our data indicate an important role for NF-AT in the faithful expression of high affinity IL-2 receptors and a close link between the TCR-mediated induction of IL-2 and IL-2 receptor chain promoters, both of which are regulated by NF-AT factors.
Key Words: interleukin 2 receptor • nuclear factor of activated T cells • transcription factors • T cells • NF-AT factors
The first two authors contributed equally to this paper.
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