IL-2 and long-term T cell activation induce physical and functional interaction between STAT5 and ETS transcription factors in human T cells.
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.
Rameil
P
P
INSERM U119, Marseille, France.
Lécine
P
P
Ghysdael
J
J
Gouilleux
F
F
Kahn-Perlès
B
B
Imbert
J
J
D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera; D007376:Interleukin-2 / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation; D008894:Milk Proteins; D008934:Mitogens / Q000494:pharmacology; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494041:ETS1 protein, human; C494069:ETS2 protein, human; D007106:Immune Sera; D007376:Interleukin-2; D008894:Milk Proteins; D008934:Mitogens; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors