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Title

Properties of transcription factors regulating interleukin-2 gene transcription through the NFAT binding site in untreated or drug-treated naive and memory T-helper cells

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Published in Blood. 1994, vol. 84, no. 8, p. 2612-21
Abstract Combining in vitro DNA binding studies and functional transcription assays in the Xenopus oocyte, we have tested the presence and functional state of transcription factors controlling the interleukin-2 (IL-2) promoter through the NFAT binding site. In naive T-helper cells, the IL-2 gene is repressed by a silencer. After first mitogenic stimulation, this silencer becomes undetectable while an activator is newly synthesized. In resting memory cells, the activator has low DNA-binding affinity and is located in the cytoplasm. However, no silencer is formed. Upon renewed cellular activation, this pre-existing activator is again targeted to the nucleus and regains function in promoting transcription. Cyclosporin A and FK506 act on two distinct levels of the IL-2 control mechanism. They prevent nuclear transport and reactivation of the performed activator in memory cells and, in naive cells, they render the silencer resistant to displacement by the activator. DNA-binding of silencer and activator from T-helper, and NFAT-1 from Jurkat cells, requires the same three G residues, but cross-linking analyses show differences in their constituent subunits. Supershift experiments show that the activator contains fra-2 and junD, whereas the silencer reacts with none of the antibodies tested.
Keywords AnimalsBase SequenceBinding SitesCyclosporine/pharmacologyDNA/chemistry/metabolismDNA-Binding Proteins/genetics/metabolismFemaleGene Expression Regulation/drug effectsHumansInterleukin-2/geneticsIonomycin/pharmacologyMolecular Sequence DataNFATC Transcription FactorsNuclear ProteinsOocytes/metabolismPromoter Regions, GeneticSimplexvirus/enzymologyT-Lymphocytes, Helper-Inducer/metabolismTacrolimus/pharmacologyTetradecanoylphorbol Acetate/pharmacologyThymidine Kinase/geneticsTranscription Factors/genetics/metabolism/pharmacologyTranscription, Genetic/drug effectsXenopus
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PMID: 7522636
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MOUZAKI, Athanasia, RUNGGER, Duri. Properties of transcription factors regulating interleukin-2 gene transcription through the NFAT binding site in untreated or drug-treated naive and memory T-helper cells. In: Blood, 1994, vol. 84, n° 8, p. 2612-21. https://archive-ouverte.unige.ch/unige:81118

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