Regulation of transcriptional activation function of rat estrogen receptor α (ERα) by novel C-terminal splice inserts.
Regulation of transcriptional activation function of rat estrogen receptor α (ERα) by novel C-terminal splice inserts.
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DOI：
10.1016/j.mce.2014.11.001
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发表时间：
2015-02-05
影响因子：
4.1
通讯作者：
Toro, Ligia
中科院分区：
文献类型：
--
作者：
Kundu, Pallob;Li, Min;Lu, Rong;Stefani, Enrico;Toro, Ligia
雌激素受体α（ERα）介导雌激素对组织的多种作用。ERα基因有8个组成型表达的外显子，已知其具有多种异构体，这些异构体通过选择性转录起始和剪接事件（包括外显子跳跃）产生。我们发现了两个插入在大鼠ERα外显子5和6之间的新外显子，它们可以独立地或串联地添加18和14个氨基酸到受体的雌激素结合/激活功能2域。它们在心脏中的转录表达是大脑、主动脉、肝脏、卵巢和子宫的三到六倍。在心脏中，从产前到成年期，随着动物的生长，新的变体增加约2倍，并且在老年动物（28个月）中略有增加。包含这些外显子产生几乎没有雌激素结合能力和减少二聚化的受体。新的变体显示出核定位，但在结合雌激素反应元件（ERE）方面效率较低，并且未能转录激活含有ERE的启动子（mSlo，KCNE 2）。因此，新的变体可以调节野生型受体功能，并可能有助于雌激素的调节作用，特别是在成熟的心脏中，它们更丰富。
Estrogen receptor α (ERα) mediates estrogen diverse actions on tissues. ERα gene has eight constitutively expressing exons and is known to have multiple isoforms generated by alternative initiation of transcription and splicing events including exon skipping. We have discovered two novel exons inserted between exon 5 and 6 of rat ERα that can add independently or in tandem 18 and 14 amino acids to the estrogen binding/activator function 2 domain of the receptor. Their transcript expression is three-to sixfold higher in heart compared to brain, aorta, liver, ovary and uterus. In heart, the new variants increased ~2 fold with animal growth from prenatal to adulthood, and had a minor increment in aged animals (28 months). Inclusion of these exons yields a receptor with practically no binding capacity for estrogen and reduced dimerization. The new variants show nuclear localization but are less efficient in binding to estrogen responsive elements (EREs) and failed to transcriptionally activate promoters containing EREs (mSlo, KCNE2). Thus, the new variants can regulate the wild-type receptor function and may contribute to the regulatory action of estrogen, especially in the maturing heart where they are more abundant.
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DOI：
10.1016/j.jsbmb.2009.10.001
发表时间：
2010-01-01
影响因子：
4.1
作者：
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影响因子：
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影响因子：
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作者：
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DOI：
10.1006/bbrc.1998.8738
发表时间：
1998-06-09
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Miksicek, RJ