The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation.

Tamara Fernández-Calero; Soledad Astrada; Alvaro Alberti; Sofía Horjales; Jean Francois Arnal; Carlos Rovira; Mariela Bollati-Fogolín; Gilles Flouriot; Mónica Marin

doi:10.1016/j.jsbmb.2014.02.016

The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation.

Tamara Fernández-Calero ^{1, 2, *} Soledad Astrada ³ Alvaro Alberti ³ Sofía Horjales ¹ Jean Francois Arnal ⁴ Carlos Rovira ⁵ Mariela Bollati-Fogolín ³ Gilles Flouriot ⁶ Mónica Marin ¹

* Auteur correspondant

1 Biochemistry-Molecular Biology

2 Bioinformatics Unit

3 Cell Biology Unit

4 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires

5 Department of Oncology

6 Irset - Institut de recherche, santé, environnement et travail

Abstract : : Until recently, synonymous mutations (which do not change amino acids) have been much neglected. Some evidence suggests that this kind of mutations could affect mRNA secondary structure or stability, translation kinetics and protein structure. To explore deeper the role of synonymous mutations, we studied their consequence on the functional activity of the estrogen receptor alpha (ERα). The ERα is a ligand-inducible transcription factor that orchestrates pleiotropic cellular effects, at both genomic and non-genomic levels in response to estrogens. In this work we analyzed in transient transfection experiments, the activity of ERα carrying the synonymous mutation Ala87, a polymorphism involving about 5-10% of the population. In comparison to the wild type receptor, our results show that ERαA87 mutation reduces the transactivation efficiency of ERα on an ERE reporter gene while its expression level remains similar. This mutation enhances 4-OHT-induced transactivation of ERα on an AP1 reporter gene. Finally, the mutation affects the subcellular localization of ERα in a cell type specific manner. It enhances the cytoplasmic location of ERα without significant changes in non-genomic effects of E2. The functional alteration of the ERαA87 determined in this work highlights the relevance of synonymous mutations for biomedical and pharmacological points of view.

Type de document :

Article dans une revue

Journal of steroid biochemistry and molecular biology , Elsevier, 2014, 143C, pp.99-104. 〈10.1016/j.jsbmb.2014.02.016〉

Domaine :

Sciences du Vivant [q-bio]

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http://www.hal.inserm.fr/inserm-01015532
Contributeur : Marie Francoise Simon <>
Soumis le : jeudi 26 juin 2014 - 16:03:36
Dernière modification le : lundi 8 octobre 2018 - 17:44:08

The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation.

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The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation.

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