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IL-2 and long-term T cell activation induce physical and functional interaction between STAT5 and ETS transcription factors in human T cells

Abstract : Activation of Stat5 by many cytokines implies that it cannot alone insure the specificity of the regulation of its target genes. We have evidenced a physical and functional interaction between members of two unrelated transcription factor families, Ets-1, Ets-2 and Stat5, which could contribute to the proliferative response to interleukin 2. Competition with GAS- and EBS-specific oligonucleotides and immunoassays with a set of anti-Stat and anti-Ets families revealed that the IL-2-induced Stat5-Ets complex recognizes several GAS motifs identified as target sites for activated Stat5 dimers. Coimmunoprecipitation experiments evidenced that a Stat5/Ets-1/2 complex is formed in vivo in absence of DNA. GST-pull down experiments demonstrated that the C-terminal domain of Ets-1 is sufficient for this interaction in vitro. Cotransfection experiments in Kit225 T cells resulted in cooperative transcriptional activity between both transcription factors in response to a combination of IL-2, PMA and ionomycin. A Stat5-Ets protein complex was the major inducible DNA-binding complex bound to the human IL-2rE GASd/EBSd motif in long-term proliferating normal human T cells activated by CD2 and CD28. These results suggest that the inducible Stat5-Ets protein interaction plays a role in the regulation of gene expression in response to IL-2 in human T lymphocytes.
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https://hal-univ-tours.archives-ouvertes.fr/hal-02427375
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Submitted on : Friday, October 29, 2021 - 3:25:45 PM
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Pascal Rameil, Patrick Lecine, Jacques Ghysdael, Fabrice Gouilleux, Brigitte Kahn-Perlès, et al.. IL-2 and long-term T cell activation induce physical and functional interaction between STAT5 and ETS transcription factors in human T cells. Oncogene, Nature Publishing Group, 2000, 19 (17), pp.2086-2097. ⟨10.1038/sj.onc.1203542⟩. ⟨hal-02427375⟩

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