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.
Métivier
Raphaël
R
Equipe d'Endocrinologie Moléculaire de la Reproduction, UMR CNRS 6026, Université de Rennes I, 35042 Rennes Cedex, France.
Gay
Frédérique A
FA
Hübner
Michael R
MR
Flouriot
Gilles
G
Salbert
Gilles
G
Gannon
Frank
F
Kah
Olivier
O
Pakdel
Farzad
F
D000230:Adenocarcinoma / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D051838:COUP Transcription Factor I; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D046911:Macromolecular Substances; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D005419:Flavonoids; D046911:Macromolecular Substances; C497589:NR2F1 protein, human; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D014157:Transcription Factors; D010768:Phosphoserine; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one