Formation of an hER alpha-COUP-TFI complex enhances hER alpha AF-1 through Ser118 phosphorylation by MAPK.

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.
Mesh Terms:
Adenocarcinoma, Breast Neoplasms, COUP Transcription Factor I, DNA, DNA-Binding Proteins, Enzyme Inhibitors, Estrogen Receptor alpha, Female, Flavonoids, Humans, Macromolecular Substances, Mitogen-Activated Protein Kinase 1, Neoplasm Proteins, Phosphorylation, Phosphoserine, Protein Binding, Protein Interaction Mapping, Protein Processing, Post-Translational, Protein Structure, Tertiary, Receptors, Estrogen, Signal Transduction, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured
EMBO J.
Date: Jul. 01, 2002
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