The interleukin 2 receptor alpha chain/CD25 promoter is a target for nuclear factor of activated T cells.
The expression of the murine interleukin (IL)-2 receptor alpha 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 alpha chain promoters, both of which are regulated by NF-AT factors.
Schuh
K
K
Institute of Pathology, University of Würzburg, D-97080 Würzburg, Germany.
Twardzik
T
T
Kneitz
B
B
Heyer
J
J
Schimpl
A
A
Serfling
E
E
D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051379:Mice; D016296:Mutagenesis; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2; D014157:Transcription Factors