Suppressive effect of aryl hydrocarbon receptor repressor on transcriptional activity of estrogen receptor alpha by protein-protein interaction in stably and transiently expressing cell lines.
Aryl hydrocarbon receptor repressor (AhRR) suppressed, in a ligand independent manner, the ability of estrogen receptor alpha (ERalpha) to enhance the transcription of heterologous estrogen-responsive reporter plasmids in transient transfection assays, as well as of endogenous estrogen-responsive genes in human breast cancer MCF-7 cells. AhRR repressed ERalpha-mediated trans-activation by interfering allosterically with the ligand-independent function of AF-1. The direct interaction between AhRR and ERalpha at the multipartite binding site of ERalpha, which ranges from a DNA binding domain to a ligand binding domain, but did not include the AF-1 moiety was confirmed by a coimmunoprecipitation assay. The AhRR/ERalpha complex was formed in the nuclear compartment and was entrapped by a cis-element in the promoter of E2-responsive genes, as determined in a chromatin immunoprecipitation assay. AhRR might play a role of co-repressor on the transcriptional activity of the ERalpha homodimer.
Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. ykanno@phar.toho-u.ac.jp
Yuichiro
Y
Kanno
Yusuke
Y
Takane
Yu
Y
Takizawa
Yoshio
Y
Inouye
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D047628:Estrogen Receptor alpha; D004967:Estrogens; D018336:Receptors, Aryl Hydrocarbon; D017471:Receptors, Interferon; D012097:Repressor Proteins; C492162:AHRR protein, human; C506487:ESR1 protein, human; C086185:IFNGR2 protein, human