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J Biol Chem, Vol. 273, Issue 8, 4416-4423, February 20, 1998
From the Departments of The human FasL enhancer region was cloned and
functionally characterized in transformed and primary T cells. Within
the 2.3 kilobase pairs of the FasL untranslated region, the distal 3' 300-base pair portion contains a single transcription initiation site
and confers basal and inducible transcriptional activity. Stimuli that
increase [Ca2+]i such as CD3 cross-linking
or ionomycin, but not activation of protein kinase C, were found to
induce FasL enhancer transcription in a cyclosporin-sensitive manner.
Moreover, calcineurin and NFAT, but not AP1, were identified as
necessary and sufficient effectors in driving FasL transcription
through an NFAT cis-acting motif (GGAAA). Additional modes of T cell
activation such as CD4 cross-linking were also found to induce NFAT
binding to the FasL enhancer region and to functionally transactivate
its transcription. These results indicate that the induction of FasL
gene transcription in T cells after CD3 or CD4 activation is
selectively mediated by calcineurin and NFAT.
Transcriptional Regulation of the Human FasL Promoter-Enhancer
Region
,§¶
Experimental Pathology and
§ Immunology, ¶ Division of Infectious Diseases, Mayo
Clinic, Rochester, Minnesota 55905
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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P. R. Mittelstadt and J. D. Ashwell Role of Egr-2 in Up-regulation of Fas Ligand in Normal T Cells and Aberrant Double-negative lpr and gld T Cells J. Biol. Chem., January 29, 1999; 274(5): 3222 - 3227. [Abstract] [Full Text] [PDF]
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S. Kasibhatla, L. Genestier, and D. R. Green Regulation of Fas-Ligand Expression during Activation-induced Cell Death in T Lymphocytes via Nuclear Factor kappa B J. Biol. Chem., January 8, 1999; 274(2): 987 - 992. [Abstract] [Full Text] [PDF]
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 P. R. Mittelstadt and J. D. Ashwell Cyclosporin A-Sensitive Transcription Factor Egr-3 Regulates Fas Ligand Expression Mol. Cell. Biol., July 1, 1998; 18(7): 3744 - 3751. [Abstract] [Full Text]
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