The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation.
(2014) In Journal of Steroid Biochemistry and Molecular Biology 143(Mar 4). p.99-104- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4383695
- author
- Fernández-Calero, Tamara ; Astrada, Soledad ; Alberti, Alvaro ; Horjales, Sofía ; Arnal, Jean Francois ; Rovira, Carlos LU ; Bollati-Fogolín, Mariela ; Flouriot, Gilles and Marin, Mónica
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Steroid Biochemistry and Molecular Biology
- volume
- 143
- issue
- Mar 4
- pages
- 99 - 104
- publisher
- Elsevier
- external identifiers
-
- pmid:24607813
- wos:000341465500011
- scopus:84896372285
- pmid:24607813
- ISSN
- 1879-1220
- DOI
- 10.1016/j.jsbmb.2014.02.016
- language
- English
- LU publication?
- yes
- id
- d87b93f0-e799-49c3-9139-b25f8d87b80b (old id 4383695)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24607813?dopt=Abstract
- date added to LUP
- 2016-04-01 09:53:54
- date last changed
- 2022-02-17 04:38:03
@article{d87b93f0-e799-49c3-9139-b25f8d87b80b,
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.}},
author = {{Fernández-Calero, Tamara and Astrada, Soledad and Alberti, Alvaro and Horjales, Sofía and Arnal, Jean Francois and Rovira, Carlos and Bollati-Fogolín, Mariela and Flouriot, Gilles and Marin, Mónica}},
issn = {{1879-1220}},
language = {{eng}},
number = {{Mar 4}},
pages = {{99--104}},
publisher = {{Elsevier}},
series = {{Journal of Steroid Biochemistry and Molecular Biology}},
title = {{The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation.}},
url = {{http://dx.doi.org/10.1016/j.jsbmb.2014.02.016}},
doi = {{10.1016/j.jsbmb.2014.02.016}},
volume = {{143}},
year = {{2014}},
}