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

✍ Scribed by Min Li-Weber; Oskar Laur; Kirsten Dern; Peter H. Krammer

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 191 KB
• Volume: 30
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/1521-4141(200002)30:2<661::aid-immu661>3.0.co;2-l

✦ Synopsis

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-O B 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-O B and SP-1 transcription factors and NF-O B is involved in transactivation of the CD95L promoter upon T cell activation. Mutations at each NF-O B 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-O B 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-O B binding to its target DNA. Our studies provide evidence that Tat-enhanced CD95L expression is regulated at least in part by the NF-O B sites of the promoter.