A newly identified response element in the CD95 ligand promoter contributes to optimal inducibility in activated T lymphocytes.
Inducible expression of CD95 ligand on activated T lymphocytes contributes to both cytotoxic effector mechanisms and peripheral T cell homeostasis. To understand better the transcriptional events that regulate this expression, we have examined the CD95 ligand promoter to determine which regions are required for its induced activity following T cell stimulation. We report here the identification of a new response element within the promoter that is required for its optimal function in activated Jurkat T cells. This region is bound by proteins contained in nuclear extracts of activated, but not resting, T cells. Multimerization of this sequence independently drives transcription in response to T cell activation, while mutation of it substantially decreases inducible promoter activity. Finally, we provide evidence that T cell activation-induced transcription of the CD95 ligand gene is regulated coordinately by this response element together with two previously defined sites for nuclear factor of activated T cells (NFAT).
Norian
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Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City 52242, USA.
Latinis
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Koretzky
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D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D053222:Fas Ligand Protein; D017930:Genes, Reporter / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000276:immunology; D019014:fas Receptor / Q000235:genetics*
D004268:DNA-Binding Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D019014:fas Receptor