Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha) that is encoded by distinct transcripts and that is able to repress hER-alpha activation function 1

Flouriot G.; Denger S.; Metivier R.Kos M.Reid G. Sonntag-Buck V.Gannon F.Brand H.

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Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha) that is encoded by distinct transcripts and that is able to repress hER-alpha activation function 1

机译：新的人类同种型的识别雌激素receptor-alpha (hER-alpha)由不同的成绩单和编码能力镇压hER-alpha激活函数1

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A new isoform of the human estrogen receptor-alpha (hER-alpha) has been identified and characterized. This 46 kDa isoform (hER alpha 46) lacks the N-terminal 173 amino acids present in the previously characterized 66 kDa isoform (hER alpha 66). hER alpha 46 is encoded by a new class of hER-alpha transcript that lacks the first coding exon (exon 1A) of the ER-alpha gene. We demonstrated that these Delta 1A hER-alpha transcripts originate from the E and F hER-alpha promoters and are produced by the splicing of exon 1E directly to exon 2. Functional analysis of hER alpha 46 showed that, in a cell context sensitive to the transactivation function AF-2, this receptor is an effective ligand-inducible transcription factor. In contrast, hER alpha 46 is a powerful inhibitor of hER alpha 66 in a cell context where the transactivating function of AF-1 predominates over AF-2. The mechanisms by which the AF-1 dominant-negative action is exerted may involve heterodimerization of the two receptor isoforms and/or direct competition for the ER-alpha DNA-binding site. hER alpha 66/ hER alpha 46 ratios change with the cell growth status of the breast carcinoma cell line MCF7, suggesting a role of hER alpha 46 in cellular proliferation. [References: 62]

机译：一个新的人类雌激素receptor-alpha同种型(hER-alpha)已被确定为特征。缺乏的氨基端173个氨基酸(她以前描述的66 kDa对碘氧基苯甲醚阿尔法66)。缺少第一的hER-alpha成绩单编码外显子1(外显子)ER-alpha基因。证明这些δ1 hER-alpha记录来自E和F hER-alpha启动子和拼接产生的外显子1 e直接向外显子2。她的α46显示,在细胞环境中敏感transactivation AF-2函数,这种受体是一种有效的ligand-inducible转录因子。66是一个强有力的抑制剂的α细胞上下文的transactivating函数在AF-2 AF-1主导。其中AF-1显性负作用是什么对可能涉及heterodimerization受体亚型和/或直接竞争ER-alpha dna结合蛋白。α46比率变化与细胞生长地位的乳腺癌MCF7细胞行,暗示她α46在细胞中的作用扩散。

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《EMBO Journal》 |2000年第17期|4688-4700|共13页
作者
Flouriot G.; Denger S.; Metivier R.Kos M.Reid G. Sonntag-Buck V.Gannon F.Brand H.;
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EMBL, Meyerhofstr 1, D-69117 Heidelberg, Germany.;

Uniquema, Gouda, The Netherlands;

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正文语种英语
中图分类分子生物学;
关键词
MCF-7 Cells; expression vector; TretinoinBreast Cancer CellHuman Mammary GlandsExonsGrowth FactorsSteroid HormoneEstrogen Receptor alphaHerculesGene regulationActivating functionEstrogen ReceptorsProtein IsoformsMCF7 cell;

机译：MCF-7细胞;表达载体;TretinoinBreast癌症CellHuman乳腺GlandsExonsGrowthFactorsSteroid HormoneEstrogen受体alphaHerculesGene regulationActivatingfunctionEstrogen ReceptorsProtein IsoformsMCF7细胞;

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Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha) that is encoded by distinct transcripts and that is able to repress hER-alpha activation function 1

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