The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation
| Autor: | Mariela Bollati-Fogolín, Mónica Marín, Carlos Rovira, Alvaro Alberti, Gilles Flouriot, Sofía Horjales, Soledad Astrada, Tamara Fernández-Calero, Jean-François Arnal |
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| Přispěvatelé: | Biochemistry-Molecular Biology, Universidad de la República [Montevideo] (UDELAR), Bioinformatics / Bioinformática [Montevideo], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Cell Biology / Biología Celular [Montevideo], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncology, Lund University [Lund]-Biomedical Centre (BMC), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universidad de la República [Montevideo] (UCUR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Biomedical Centre (BMC)-Lund University [Lund], Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Simon, Marie Francoise |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Silent mutation
Transcriptional Activation Transcription Genetic Endocrinology Diabetes and Metabolism [SDV]Life Sciences [q-bio] Clinical Biochemistry Blotting Western Fluorescent Antibody Technique Biology medicine.disease_cause Real-Time Polymerase Chain Reaction Response Elements Biochemistry Transactivation Endocrinology medicine Humans RNA Messenger Molecular Biology Transcription factor Estrogen receptor beta Cellular localization Genetics Mutation Reverse Transcriptase Polymerase Chain Reaction Estrogen Receptor alpha Estrogens Cell Biology Hep G2 Cells [SDV] Life Sciences [q-bio] Transcription Factor AP-1 Gene Expression Regulation Molecular Medicine Synonymous substitution Estrogen receptor alpha HeLa Cells Protein Binding |
| Zdroj: | Journal of Steroid Biochemistry and Molecular Biology Journal of Steroid Biochemistry and Molecular Biology, 2014, 143C, pp.99-104. ⟨10.1016/j.jsbmb.2014.02.016⟩ Journal of Steroid Biochemistry and Molecular Biology, Elsevier, 2014, 143C, pp.99-104. ⟨10.1016/j.jsbmb.2014.02.016⟩ |
| ISSN: | 0960-0760 |
| Popis: | International audience; : 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. |
| Databáze: | OpenAIRE |
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