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Cyclosporin A and FK506 prevent the derepression of the IL-2 gene in mitogen-induced primary T lymphocytes

Published in Cytokine. 1992, vol. 4, no. 2, p. 151-160
Abstract In resting primary T lymphocytes the interleukin 2 (IL-2) gene is silenced by a repressor binding to the Pud element spanning positions −292 to −264 upstream of the cap site. Upon T-cell activation, this silencer is displaced by a positive transcription factor (TF) and the gene is derepressed and transcribed. Cyclosporin A (CsA) and FK506 interfere with normal derepression of the IL-2 gene. Both drugs exert no direct effect on basal transcription of the IL-2 or control viral genes. Direct addition does not abolish the active state of positive TFs present in proteins from activated T cells. However, if T cells are activated in the presence of either drug, their proteins not only fail to derepress, but efficiently and irreversibly silence IL-2 transcription. DNA-protein binding data show that proteins present in drug-treated cells form retarded complexes corresponding in size to the silencer and positive TF. Thus, in drug-treated cells a functional silencer persists, and a positive TF-like factor appears which is functionally abnormal. Moreover, drug-treated T cells appear to form a component that prevents functioning of normal positive TF.
Keywords Gene regulationSilencerTrans-activationTranscription assayXenopus laevis oocyte
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Swiss National Science Foundation: 3.128654.90
Swiss National Science Foundation: 3.586.087
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MOUZAKI, Athanasia et al. Cyclosporin A and FK506 prevent the derepression of the IL-2 gene in mitogen-induced primary T lymphocytes. In: Cytokine, 1992, vol. 4, n° 2, p. 151-160. doi: 10.1016/1043-4666(92)90050-2 https://archive-ouverte.unige.ch/unige:138560

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