Transcriptional suppression of the estrogen receptor by truncated estrogen receptor-alpha.
The estrogen receptor (ER) is composed of six major functional domains - the A/B domain as the activation function 1 domain, domain C as the DNA-binding domain, domain D as a hinge domain, and domain E/F as the ligand-dependent transcriptional domains. A novel protein (designated as SRB-RGS) that interacted with domains C and D of ER alpha (ER alpha C/D) repressed the transcriptional activity of ER alpha. In this study, we have examined whether ER alpha C/D releases transcriptional suppression of ER alpha by intrinsic SRB-RGS. The expression vector of ER alpha C/D was transfected to the human cancer cell, KPL-1, which expressed the intrinsic ER. Unexpectedly, transcriptional suppression of ER by ER alpha C/D was observed. COS-7 cells, which have no intrinsic ER, showed a similar suppression of ER alpha by co-transfection of ER alpha and ER alpha C/D. The DNA-binding and the estrogen-binding activities of ER alpha decreased on co-transfection of ER alpha C/D, suggesting a decrease in the receptor protein itself. It is likely that the degradation of ER by co-transfection caused the transcriptional suppression of the ER.
Department of Biochemistry, Kawasaki Medical School, Kurashiki, Okayama, Japan. ikeda@bcc.kawasaki-m.ac.jp
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Ikeda
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Okai
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Miyoshi
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Tone
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Minatogawa
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D047628:Estrogen Receptor alpha; D006801:Humans; D008856:Microscopy, Fluorescence; D009841:Oligonucleotides; D010957:Plasmids / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics*; D013489:Suppression, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D009841:Oligonucleotides; D011960:Receptors, Estrogen; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase