Interaction between transcription factor, basal transcription factor 3, and the NH2-terminal domain of human estrogen receptor alpha.
The estrogen receptor (ER), like other members of the nuclear receptor superfamily, possesses two separate transcriptional activation functions, AF-1 and AF-2. Although a variety of coactivators and corepressors of AF-2 have been identified, less is known of the mechanism of action of AF-1. We have used the yeast two-hybrid system to isolate a cDNA coding for a protein that binds specifically to the AF-1 region of human ERalpha. This cDNA codes for the transcription factor basal transcription factor 3 (BTF3). The specificity of the interaction between BTF3 and ERalpha has been confirmed in vivo and in vitro. Transient transfection experiments reveal that overexpression of BTF3 modulates the transcriptional response of reporter genes to ERalpha. BTF3 interacts with ERalpha that has been activated either by 17beta-estradiol (ligand-dependent activation) or by epidermal growth factor (ligand-independent activation). The effects of BTF3 on the reporter genes requires the presence of ERalpha containing an active AF-1 function. BTF3 may be a component of the mechanism by which the AF-1 function of ERalpha stimulates gene transcription.
Green
Chris D
CD
Centre for Cancer Research and Cell Biology, Queen's University Belfast, University Floor, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, United Kingdom.
Thompson
Paul D
PD
Johnston
Patrick G
PG
El-Tanani
Mohamed K
MK
D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; C063552:transcription factor BTF3; D004958:Estradiol; D004815:Epidermal Growth Factor