کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8338667 | 1541007 | 2014 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The transcriptional activities and cellular localization of the human estrogen receptor alpha are affected by the synonymous Ala87 mutation
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کلمات کلیدی
EREERK 1/24-OHT17β-estradiol - 17β استرادیولSERMs - SERM هاEstrogen - استروژنICI - اینجاICI 182,780 - اینجا 182،780Synonymous mutations - جهش های معروفestrogen response element - عنصر پاسخ استروژنwild type - نوع وحشیextracellular-signal-regulated kinase - کیناز تنظیم شده خارج سلولی سیگنالEstrogen receptor - گیرنده استروژنEstrogen receptor alpha - گیرنده استروژن آلفا
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 143, September 2014, Pages 99-104
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 143, September 2014, Pages 99-104
نویسندگان
Tamara Fernández-Calero, Soledad Astrada, Álvaro Alberti, SofÃa Horjales, Jean Francois Arnal, Carlos Rovira, Mariela Bollati-FogolÃn, Gilles Flouriot, Mónica Marin,