Regulation of transcriptional activity of the murine CD40 ligand promoter in response to signals through TCR and the costimulatory molecules CD28 and CD2.
We have analyzed the murine CD40 ligand promoter with regard to stimulation of transcriptional activity in Jurkat T cells after signaling via the TCR and the costimulatory molecules CD28 and CD2. TCR engagement was necessary for the induction of transcriptional activity from the CD40 ligand promoter, and costimulation through either CD28 or CD2 further increased the activity. Analysis of promoter deletants showed that the DNA elements needed for transcriptional activity induced by costimulatory molecules were located within two regions containing previously identified transcription factor NFAT sites. Further studies of the proximal NFAT site showed that it was not dependent on AP-1 binding for transcriptional activity induced by costimulation through CD28. Instead, a region between the TATA box and the proximal NFAT site was shown to bind proteins of the early growth response family and to contribute to NFAT-mediated transcriptional activation.
Section for Immunology, Department of Cell and Molecular Biology, Lund University, Lund, Sweden. hanna.lindgren@immuno.lu.se
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Lindgren
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Axcrona
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Leanderson
D020413:3' Untranslated Regions / Q000235:genetics / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D018801:CD2 Antigens / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology*; D023201:CD40 Ligand / Q000235:genetics*; D016466:CHO Cells; D002467:Cell Nucleus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics; D019169:Jurkat Cells; D008024:Ligands; D051379:Mice; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D016385:TATA Box / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation / Q000276:immunology*; D014162:Transfection
D020413:3' Untranslated Regions; D018801:CD2 Antigens; D018106:CD28 Antigens; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D007376:Interleukin-2; D008024:Ligands; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D023201:CD40 Ligand