Abstract
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.
Keywords
NFATFas receptorBiologyTranscription factorFas ligandCell biologyMolecular biologyCytokine receptorSignal transductionApoptosisGeneProgrammed cell deathGenetics
Affiliated Institutions
Related Publications
A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand-induced apoptosis.
Dendritic cells (DC), the most efficient antigen-presenting cells, are well equipped for activation of naive CD4+ T cells by their expression of high levels of major histocompat...
The c-Jun N-Terminal Kinase Cascade Plays a Role in Stress-Induced Apoptosis in Jurkat Cells by Up-Regulating Fas Ligand Expression
Abstract T lymphocytes undergo apoptosis in response to cellular stress, including UV exposure and gamma irradiation. However, the mechanism by which stress stimuli induce apopt...
Apoptosis induced by DNA damage O6-methylguanine is Bcl-2 and caspase-9/3 regulated and Fas/caspase-8 independent.
In the therapy of various kinds of tumors, methylating agents generating O6-methylguanine (O6MeG) in DNA are used. We studied the molecular mechanism of cell death induced by th...
Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells
Activated T lymphocytes accumulate early in atheroma formation and persist at sites of lesion growth and rupture, suggesting that they may play an important role in the pathogen...
Inhibition of death receptor signals by cellular FLIP
The widely expressed protein Fas is a member of the tumour necrosis factor receptor family which can trigger apoptosis. However, Fas surface expression does not necessarily rend...
Publication Info
- Year
- 1997
- Type
- article
- Volume
- 272
- Issue
- 50
- Pages
- 31427-31434
- Citations
- 217
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
217
OpenAlex
Cite This
Kevin Latinis,
Lyse A. Norian,
Steve Eliason
et al.
(1997).
Two NFAT Transcription Factor Binding Sites Participate in the Regulation of CD95 (Fas) Ligand Expression in Activated Human T Cells.
Journal of Biological Chemistry
, 272
(50)
, 31427-31434.
https://doi.org/10.1074/jbc.272.50.31427
Identifiers
- DOI
- 10.1074/jbc.272.50.31427