Activation function 2 mediates dioxin-induced recruitment of estrogen receptor alpha to CYP1A1 and CYP1B1.
We investigated the role of the activation function 1 (AF1) and AF2 domains of estrogen receptor alpha (ERalpha) in mediating dioxin-dependent recruitment of ERalpha to cytochrome P4501A1 (CYP1A1) and CYP1B1 in HuH-7 human hepatoma cells. Dioxin-induced recruitment of ERalpha wildtype (ERalpha-WT) and an ERalpha AF1 deletion mutant (ERalpha-DeltaAF1), but not ... a transcriptional inactive AF2 mutant (ERalpha-AF2mut) to CYP1A1 and CYP1B1. Direct interactions between AHR and the AF1 and AF2 domains of ERalpha were observed, and were independent of mutations in the AF2. Expression of ERalpha-WT increased dioxin-induced CYP1A1 and CYP1B1-regulated reporter activity, and CYP1A1 and CYP1B1 mRNA levels. However, no increases in gene expression above vector controls were observed in cells transfected with ERalpha-DeltaAF1 or ERalpha-AF2mut. Our data show that the AF2 domain contributes to dioxin-induced recruitment of ERalpha to AHR target genes, but that both the AF1 and AF2 domains are required for ERalpha-dependent increases in AHR activity.
Mesh Terms:
Aryl Hydrocarbon Hydroxylases, Cell Line, Tumor, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1B1, Cytochrome P-450 Enzyme System, Estrogen Receptor alpha, Gene Expression Regulation, Enzymologic, Humans, Protein Structure, Tertiary, Receptors, Aryl Hydrocarbon, Sequence Deletion, Tetrachlorodibenzodioxin
Aryl Hydrocarbon Hydroxylases, Cell Line, Tumor, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1B1, Cytochrome P-450 Enzyme System, Estrogen Receptor alpha, Gene Expression Regulation, Enzymologic, Humans, Protein Structure, Tertiary, Receptors, Aryl Hydrocarbon, Sequence Deletion, Tetrachlorodibenzodioxin
Biochem. Biophys. Res. Commun.
Date: Jul. 24, 2009
PubMed ID: 19460354
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