Identification of LIL-STAT in monocytic leukemia cells and monocytes after stimulation with interleukin-6 or interferon gamma.
In acute myelogenous leukemia (AML) and adult T-cell leukemia, it has been demonstrated that the transcription factor LIL-STAT is constitutively activated. To identify and characterize this unknown LIL-STAT protein, electrophoretic mobility shift assay (EMSA) and oligoprecipitation assays were performed by using lipopolysaccharide/interleukin-1 (IL-1)-responsive element (LILRE) oligonucleotide probes. EMSA demonstrated a significant increase in LIL-STAT binding to the LILRE oligonucleotides after interferon gamma (IFN-gamma) and IL-6 stimulation of THP-1 cells. In unstimulated THP-1 and AML cells, LILRE oligonucleotide probes bound only to STAT1 alpha and beta isoforms. The LILRE element showed a significant increase in binding of both alpha and beta isoforms of STAT1 and STAT3 upon IFN-gamma and IL-6 stimulation. Similar results were observed with human monocytes upon IL-6 or IFN-gamma stimulation. These studies indicate that LIL-STAT consists of STAT1 and STAT3 proteins that bind to the LILRE DNA consensus site in a stimulus-dependent way.
Lemmink
H H
HH
Division of Hematology, Department of Internal Medicine, Academic Hospital Groningen, The Netherlands.
Tuyt
L
L
Knol
G
G
Krikke
E
E
Vellenga
E
E
D001665:Binding Sites; D011232:Chemical Precipitation; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000378:metabolism; D020218:Response Elements; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007375:Interleukin-1; D015850:Interleukin-6; C114046:LIL-Stat transcription factor; D008070:Lipopolysaccharides; D015345:Oligonucleotide Probes; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma