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

Article Article scientifique Article Cyclosporin A and FK506 prevent the derepression of the IL-2 gene in mitogen-induced primary T lymphocytes eng 1992 author Mouzaki Athanasia 24222 author Dai-Luo Ying 21887 author Weil Roger 25112 author Rungger Duri 25122 151-160 10.1016/1043-4666(92)90050-2 1043-4666 https://linkinghub.elsevier.com/retrieve/pii/1043466692900502 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. Gene regulation Silencer Trans-activation Transcription assay Xenopus laevis oocyte Dewey 570 Swiss National Science Foundation 3.128654.90 CH Swiss National Science Foundation 3.586.087 CH 43 Département de biologie moléculaire 161 false Cytokine 4 2 1fe2f16a-1cf7-461f-9a99-d9e082340d37 Article (Published version) Restricted 1-s2.0-1043466692900502-main.pdf 1473822 application/pdf restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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Cyclosporin A and FK506 prevent the derepression of the IL-2 gene in mitogen-induced primary T lymphocytes	Cytokine			1992	297	0

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