Estrogen regulation of human with-no-lysine (K) kinase-4 gene expression involves AP-1 transcription factor

Estrogen regulation of human with-no-lysine (K) kinase-4 gene expression involves AP-1 transcription factor
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雌激素对人无赖氨酸 (K) 激酶 4 基因表达的调节涉及 AP-1 转录因子

DOI:
10.1016/j.mce.2010.10.006
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发表时间:
2011-01
影响因子:
4.1
通讯作者:
Li, Chunyi
Li, Chunyi
中科院分区:
医学2区
文献类型:
--
作者:
Zhao, Yanyan;Li, Wei;Zhang, Yuanyuan;Li, Chunyi

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无赖氨酸(K)激酶-4(WNK 4)是一种丝氨酸/苏氨酸蛋白激酶,在血压和电解质稳态调节中起着至关重要的作用。雌激素作为生理功能的重要调节因子,是否调节人WNK 4(hWNK 4)基因的表达尚不清楚。本研究采用实时荧光定量PCR方法检测了17β-雌二醇(E2)和雌激素受体α(ERα)对人胚肾293细胞(HEK 293)hWNK 4 mRNA表达的影响。对截短的hWNK 4启动子的荧光素酶活性分析表明,从-216到-202的调节区对于基础转录活性和对E2/ERα的应答是必需的。使用电泳迁移率变动分析和染色质免疫沉淀分析,我们在-215/-205位置鉴定了激活蛋白-1(AP-1)元件,E2/ERα增强了AP-1与该元件的结合。Western blot分析显示E2/ERα可上调AP-1蛋白表达。此外,染色质免疫共沉淀和染色质免疫共沉淀实验显示ERα和AP-1在HEK 293细胞中存在直接的相互作用。总之,这些数据证明E2/ERα部分通过AP-1与hWNK 4启动子结合来调节hWNK 4表达。
With-no-lysine (K) kinase-4 (WNK4) is a serine/threonine protein kinase and plays a crucial role in the regulation of blood pressure and electrolyte homeostasis. Whether or not estrogen, an important regulator of physiologic functions, modulates human WNK4 (hWNK4) gene expression is unknown. In the current study, real-time PCR assay showed that 17β-estradiol (E2) with estrogen receptor alpha (ERα) suppressed the level of hWNK4 mRNA in cultured human embryo kidney 293 cells (HEK293). Luciferase activity analysis of the truncated hWNK4 promoters indicated that a regulatory region from −216 to −202 is essential for the basal transcriptional activity and response to E2/ERα. Using an electrophoresis mobility shift assay and a chromatin immunoprecipitation assay, we identified an activator protein-1 (AP-1) element at position −215/−205, to which AP-1 binding was enhanced by E2/ERα. Accordingly, AP-1 protein was increased by E2/ERα using Western blot analysis. Moreover, re-chromatin-immunoprecipitation and co-immunoprecipitation assays showed a direct interaction between ERα and AP-1 in HEK293 cells. In summary, these data document that E2/ERα regulates hWNK4 expression partly through AP-1 binding to the hWNK4 promoter.
DOI: --
发表时间: 1994-06
期刊: The Journal of biological chemistry
影响因子: --
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发表时间: 2004-03
影响因子: 11.1
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发表时间: 2008
影响因子: 3.5
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DOI: 10.1210/endo.139.4.5870
发表时间: 1998-04
期刊: Endocrinology
影响因子: 4.8
作者:
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