A regulatory element in the CD95 (APO-1/Fas) ligand promoter is essential for responsiveness to TCR-mediated activation

Eur J Immunol. 1998 Aug;28(8):2373-83. doi: 10.1002/(SICI)1521-4141(199808)28:08<2373::AID-IMMU2373>3.0.CO;2-T.


Expression of the CD95 (APO-1/Fas) ligand (CD95L) in activated T cells is a major cause of T cell activation-induced apoptosis. To study the molecular mechanisms of transcriptional control of CD95L expression in T cells, we investigated the human CD95L promoter in Jurkat T cells. Deletion studies revealed that the CD95L proximal promoter sequence from -220 to the transcription start site is essential for T cell stimulation-induced expression of CD95L. In this study, we discovered a novel regulatory element located at -120 of the CD95L promoter which contains DNA binding sites for SP-1 and a yet unknown inducible factor. Mutation analysis demonstrated that binding of the inducible factor to the -120 region is crucial for the biological function of the CD95L promoter upon T cell stimulation. The DNA sequence at -120 also contains two DNA motifs homologous to the binding site for NF-AT. NF-AT does not directly bind to this element. However, cotransfection studies with an NF-AT expression vector showed that NF-AT may confer a strong inducible activity to the CD95L promoter at this regulatory region. Our data also show that the immunosuppressive agent cyclosporin A down-regulates CD95L transcription by inhibiting the function of this positive regulatory element.

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / immunology
  • Base Sequence
  • Binding Sites / genetics
  • Cyclosporine / pharmacology
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Fas Ligand Protein
  • Gene Expression Regulation
  • Genes, Regulator
  • Humans
  • Ionomycin / pharmacology
  • Jurkat Cells
  • Ligands
  • Lymphocyte Activation
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology*
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Promoter Regions, Genetic*
  • Receptors, Antigen, T-Cell / metabolism*
  • Sp1 Transcription Factor / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factors / metabolism
  • Transfection
  • fas Receptor / metabolism*


  • DNA-Binding Proteins
  • FASLG protein, human
  • Fas Ligand Protein
  • Ligands
  • Membrane Glycoproteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • Sp1 Transcription Factor
  • Transcription Factors
  • fas Receptor
  • Ionomycin
  • Cyclosporine
  • DNA
  • Tetradecanoylphorbol Acetate