The aryl hydrocarbon receptor interacts with estrogen receptor alpha and orphan receptors COUP-TFI and ERRalpha1.
Article Details
- CitationCopy to clipboard
Klinge CM, Kaur K, Swanson HI
The aryl hydrocarbon receptor interacts with estrogen receptor alpha and orphan receptors COUP-TFI and ERRalpha1.
Arch Biochem Biophys. 2000 Jan 1;373(1):163-74.
- PubMed ID
- 10620335 [ View in PubMed]
- Abstract
The molecular mechanisms underlying the apparent "cross-talk" between estrogen receptor (ER)- and arylhydrocarbon receptor (AHR)-mediated activities are unknown. To determine how AHR ligand 2, 3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may inhibit ER action and, conversely, to examine how 17-beta-estradiol (E(2)) affects AHR activity, we examined discrete activities of each receptor, i.e., protein-protein interactions, DNA binding, and transcriptional activation. We report that AHR interacts directly with ERalpha, COUP-TF, and ERRalpha1, in a ligand-specific manner in vitro. Unoccupied or beta-napthoflavone (beta-NF)-occupied AHR showed stronger interaction with ERalpha, COUP-TF, and ERRalpha1 than when AHR was occupied by the partial antagonist alpha-naphthoflavone (alpha-NF), indicating a role for ligand in AHR interaction with these proteins. We also report that AHR interacts with COUP-TF in transfected CV-1 cells. In contrast, the AHR nuclear translocator protein (ARNT) did not interact with COUP-TF, ERRalpha1, or ERalpha. We next examined the interaction of either ERalpha or COUP-TF with a consensus xenobiotic response element (XRE). Purified ERalpha did not bind the consensus XRE, but COUP-TFI bound the consensus XRE, suggesting a role for COUP-TF as a AHR/ARNT competitor for XRE binding. In transiently transfected MCF-7 human breast cancer cells, overexpression of COUP-TFI inhibited TCDD-activated reporter gene activity from the CYP1A1 promoter. TCDD inhibited estradiol (E(2))-activated reporter gene activity from a consensus ERE and from the EREs in the pS2 and Fos genes, and COUP-TFI did not block the antiestrogenic activity of TCDD. The specific interaction of COUP-TF with XREs and AHR together with the inhibition of TCDD-induced gene expression by COUP-TF suggests that COUP-TF may regulate AHR action both by direct DNA binding competition and through protein-protein interactions.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions beta-Naphthoflavone Aryl hydrocarbon receptor Protein Humans UnknownAgonistDetails beta-Naphthoflavone COUP transcription factor 1 Protein Humans UnknownNot Available Details beta-Naphthoflavone Estrogen receptor alpha Protein Humans UnknownNot Available Details beta-Naphthoflavone Steroid hormone receptor ERR1 Protein Humans UnknownNot Available Details - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Estradiol Approved Investigational Vet Approved FOS 2353 upregulated Estradiol results in increased expression of FOS mRNA 14q24.3 Estradiol Approved Investigational Vet Approved TFF1 7031 upregulated Estradiol results in increased expression of TFF1 mRNA 21q22.3