Abstract
The enhancement of the human estrogen receptor alpha (hER alpha, NR3A1) activity by the orphan nuclear receptor COUP-TFI is found to depend on the establishment of a tight hER alpha-COUP-TFI complex. Formation of this complex seems to involve dynamic mechanisms different from those allowing hER alpha homodimerization. Although the hER alpha-COUP-TFI complex is present in all cells tested, the transcriptional cooperation between the two nuclear receptors is restricted to cell lines permissive to hER alpha activation function 1 (AF-1). In these cells, the physical interaction between COUP-TFI and hER alpha increases the affinity of hER alpha for ERK2/p42(MAPK), resulting in an enhanced phosphorylation state of the hER alpha Ser118. hER alpha thus acquires a strengthened AF-1 activity due to its hyperphosphorylation. These data indicate an alternative interaction process between nuclear receptors and demonstrate a novel protein intercommunication pathway that modulates hER alpha AF-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / pathology
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Breast Neoplasms / pathology
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COUP Transcription Factor I
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DNA / metabolism
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DNA-Binding Proteins / metabolism*
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Enzyme Inhibitors / pharmacology
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Estrogen Receptor alpha
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Female
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Flavonoids / pharmacology
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Humans
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Macromolecular Substances
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism*
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Neoplasm Proteins / metabolism
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Phosphorylation
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Phosphoserine / metabolism
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Protein Binding
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Protein Interaction Mapping
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Protein Processing, Post-Translational*
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Protein Structure, Tertiary
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Receptors, Estrogen / metabolism*
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Signal Transduction
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Transcription Factors / metabolism*
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Transcription, Genetic
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Tumor Cells, Cultured
Substances
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COUP Transcription Factor I
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DNA-Binding Proteins
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Enzyme Inhibitors
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Estrogen Receptor alpha
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Flavonoids
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Macromolecular Substances
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NR2F1 protein, human
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Neoplasm Proteins
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Receptors, Estrogen
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Transcription Factors
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Phosphoserine
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DNA
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Mitogen-Activated Protein Kinase 1
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one