T cell activation-induced and HIV Tat-enhanced CD95(APO-1 / Fas) ligand transcription involves NF-κB

CD95(APO-1 / Fas) ligand (CD95L) gene expression is critically involved in activation-induced T cell apoptosis. We and other have previously shown that HIV-1 Tat which is essential for efficient HIV gene expression sensitizes CD95-mediated apoptosis and up-regulates CD95L expression in T cells. In t...

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Bibliographic Details
Main Authors: Li-Weber, Min (Author) , Krammer, Peter H. (Author)
Format: Article (Journal)
Language:English
Published: 28 August 2000
In: European journal of immunology
Year: 2000, Volume: 30, Issue: 2, Pages: 661-670
ISSN:1521-4141
DOI:https://doi.org/10.1002/1521-4141(200002)30:2<661::AID-IMMU661>3.0.CO;2-L
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/https://doi.org/10.1002/1521-4141(200002)30:2<661::AID-IMMU661>3.0.CO;2-L
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/1521-4141%28200002%2930%3A2%3C661%3A%3AAID-IMMU661%3E3.0.CO%3B2-L
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Author Notes:Min Li‐Weber, Oskar Laur, Kirsten Dern and Peter H. Krammer
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Summary:CD95(APO-1 / Fas) ligand (CD95L) gene expression is critically involved in activation-induced T cell apoptosis. We and other have previously shown that HIV-1 Tat which is essential for efficient HIV gene expression sensitizes CD95-mediated apoptosis and up-regulates CD95L expression in T cells. In the present study we have investigated the regulatory mechanism for CD95L expression. Two NF-κB binding sites are localized at − 537 to − 521 and − 57 to − 47 (relative to the transcription start site) of the human CD95L promoter. We show that both elements bind to NF-κB and SP-1 transcription factors and NF-κB is involved in transactivation of the CD95L promoter upon T cell activation. Mutations at each NF-κB site by two base pair substitutions resulted in 30 - 70 % reduction of the promoter activity. The effect of Tat on the human CD95L promoter activity was mapped to the same sites. Mutation of each NF-κB site also impaired the effect of Tat on CD95L promotor activity. We also show that ectopic expression of Tat protein in Jurkat T cells greatly increases NF-κB binding to its target DNA. Our studies provide evidence that Tat-enhanced CD95L expression is regulated at least in part by the NF-κB sites of the promoter.
Item Description:Gesehen am 26.04.2021
Physical Description:Online Resource
ISSN:1521-4141
DOI:https://doi.org/10.1002/1521-4141(200002)30:2<661::AID-IMMU661>3.0.CO;2-L