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

• Verfasst von: Li-Weber, Min [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: T cell activation-induced and HIV Tat-enhanced CD95(APO-1 / Fas) ligand transcription involves NF-κB
• Verf.angabe: Min Li‐Weber, Oskar Laur, Kirsten Dern and Peter H. Krammer
• E-Jahr: 2000
• Jahr: 28 August 2000
• Umfang: 10 S.
• Teil: volume:30
• Teil: year:2000
• Teil: number:2
• Teil: pages:661-670
• Teil: extent:10
• Fussnoten: Gesehen am 26.04.2021
• Titel Quelle: Enthalten in: European journal of immunology
• Ort Quelle: Weinheim : Wiley-VCH, 1971
• Jahr Quelle: 2000
• Band/Heft Quelle: 30(2000), 2, Seite 661-670
• ISSN Quelle: 1521-4141
• DOI: doi:10.1002/1521-4141(200002)30:2<661::AID-IMMU661>3.0.CO;2-L
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: AIDS
• Sach-SW: Apoptosis
• Sach-SW: CD95(APO-1 / Fas) ligand promoter
• Sach-SW: T cell
• K10plus-PPN: 1755938101

Abstract

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.