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Volume 272, Number 50, Issue of December 12, 1997
pp. 31427-31434
(Received for publication, July 11, 1997, and in revised form, September 24, 1997)
From the Antigen receptor engagement on T lymphocytes
activates transcription factors important for stimulating cytokine gene
expression. This is critical for clonal expansion of antigen-specific T
cells and propagation of immune responses. Additionally, under some conditions antigen receptor stimulation initiates apoptosis of T
lymphocytes through the induced expression of CD95 ligand and its
receptor. Here we demonstrate that the transcription factor, NFAT,
which is critical for the inducible expression of many cytokine genes,
also plays a critical role in the regulation of T cell receptor-mediated CD95 ligand expression. Two sites within the CD95
ligand promoter, identified through DNase I footprinting, bind NFAT
proteins from nuclear extracts of activated T cells. Although both
sites appear important for optimal expression of CD95 ligand in
activated T cells, mutational analysis suggests that the distal NFAT
site plays a more significant role. Furthermore, these sites do not
appear to be required for constitutive CD95 ligand expression in
Sertoli cells.
Two NFAT Transcription Factor Binding Sites Participate in
the Regulation of CD95 (Fas) Ligand Expression in Activated Human T
Cells
,
,§¶
Interdisciplinary Graduate Program in
Immunology and Departments of § Internal Medicine and
¶ Physiology and Biophysics, University of Iowa,
Iowa City, Iowa 52242
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