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Molecular Pharmacology

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Research ArticleArticle

Functional Differences between the Amino-Terminal Domains of Estrogen Receptors α and β

Franck Delaunay, Katarina Pettersson, Michel Tujague and Jan-Åke Gustafsson
Molecular Pharmacology September 2000, 58 (3) 584-590; DOI: https://doi.org/10.1124/mol.58.3.584
Franck Delaunay
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Katarina Pettersson
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Michel Tujague
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Jan-Åke Gustafsson
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Abstract

Human estrogen receptors α (ERα) and β (ERβ) are ligand-inducible transcription factors that are highly homologous in their central DNA-binding and carboxyl-terminal ligand-binding domains. In contrast, there is very little conservation between ERα and ERβ in the amino-terminal domain. Using different human cell lines, we show that wild-type ERβ transcriptional activity is lower or similar to that of ERα, depending on the cell type. Deletion of the amino-terminal domain in both ER subtypes resulted in no or a lower decrease of transcriptional activity of ERβ compared with ERα, suggesting that the ERβ amino-terminal domain contains a weaker transcriptional activation function-1. Using ERα and ERβ deletion mutants, we showed that the amino-terminal transcriptional activity of ERβ maps to amino acids 1-31. Interestingly, this domain contains a six amino-acid motif (amino acids 5–10 in human ERβ) that is part of the ERα-activation function-1 region (amino acids 49–54 in human ERα) and highly conserved among all mammalian ERα amino-terminal domains. Despite this similarity between the two ER subtypes, no autonomous and ligand-independent activity of the ERβ-amino-terminal domain was observed in yeast and mammalian cells in contrast to ERα. This study provides a molecular basis for the difference in transcriptional activity between ERα and ERβ and establishes that ERβ contains a structurally and functionally restricted amino-terminal transcriptional activity.

Footnotes

    • Received March 3, 2000.
    • Accepted June 6, 2000.
  • Send reprint requests to: Jan-Åke Gustafsson, Department of Medical Nutrition, NOVUM, Karolinska Institute, S-141 86 Huddinge, Sweden. E-mail: jan-ake.gustafsson{at}csb.ki.se

  • ↵1 Present address: Ecole Normale Supérieure, CNRS UMR 5665, 46 allée d'Italie, Lyon 69364 Cedex, France.

  • This work was supported by grants from the Swedish Cancer Society and from KaroBio AB (to J.-Å.G.).

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 58 (3)
Molecular Pharmacology
Vol. 58, Issue 3
1 Sep 2000
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Research ArticleArticle

Functional Differences between the Amino-Terminal Domains of Estrogen Receptors α and β

Franck Delaunay, Katarina Pettersson, Michel Tujague and Jan-Åke Gustafsson
Molecular Pharmacology September 1, 2000, 58 (3) 584-590; DOI: https://doi.org/10.1124/mol.58.3.584

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Research ArticleArticle

Functional Differences between the Amino-Terminal Domains of Estrogen Receptors α and β

Franck Delaunay, Katarina Pettersson, Michel Tujague and Jan-Åke Gustafsson
Molecular Pharmacology September 1, 2000, 58 (3) 584-590; DOI: https://doi.org/10.1124/mol.58.3.584
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