An activator protein-1 complex mediates epidermal growth factor regulation of equine glycoprotein alpha subunit expression in trophoblast cells.
An activator protein-1 complex mediates epidermal growth factor regulation of equine glycoprotein alpha subunit expression in trophoblast cells.
复制标题
激活蛋白 1 复合物介导表皮生长因子对滋养层细胞中马糖蛋白 α 亚基表达的调节。
DOI：
10.1095/biolreprod.101.001057
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发表时间：
2002
影响因子：
3.6
通讯作者：
Wolfe,MichaelW
中科院分区：
文献类型：
--
作者：
Thway,TheingiM;Wolfe,MichaelW
马和灵长类动物是已知表达胎盘激素绒毛膜促性腺激素（CG）的唯一物种。CG是异源二聚体糖蛋白家族的成员，由α亚基连接至糖蛋白特异性β亚基组成。以前，我们已经报道了表皮生长因子（EGF）通过蛋白激酶C（PKC）/丝裂原活化蛋白激酶（MAPK）信号转导途径调节滋养层中马糖蛋白激素α亚基启动子。本研究探讨EGF诱导马糖蛋白α亚基基因表达的调控元件/因子。利用5′端缺失突变，我们已经将马α亚基基因的主要EGF/PKC反应区定位在转录起始位点上游的-2039到-2032碱基对之间。该区域内的序列包含激活蛋白1（AP-1）样应答元件（TGAATCA），并且与共有AP-1（TGAC/GTCA）应答元件相似。该元件似乎优先与c-fos/JunD异二聚体相互作用。EGF刺激诱导c-fos和JunD与该元件结合，随后提高启动子活性。总之，EGF/PKC/MAPK信号转导通路通过位于滋养层中马糖蛋白α亚基启动子的−2039至−2032之间的独特调控元件调节马糖蛋白α亚基基因表达，并涉及AP-1复合物。
Equids and primates are the only species known to express the placental hormone chorionic gonadotropin (CG). CG is a member of the heterodimeric glycoprotein family and is composed of an α subunit linked to a hormone-specific β subunit. Previously, we have reported that epidermal growth factor (EGF) regulates the equine glycoprotein hormone α subunit promoter through a protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) signal transduction pathway in trophoblasts. The current study investigates the regulatory element/factors involved in the induction of equine glycoprotein α subunit gene expression by EGF. Using 5′ deletion mutagenesis, we have delineated the primary EGF/PKC responsive region of the equine α subunit gene to be located between −2039 to −2032 base pairs upstream of the transcriptional start site. The sequence within this region contains an activator protein 1 (AP-1)-like response element (TGAATCA) and is similar to a consensus AP-1 (TGAC/GTCA) response element. This element appeared to preferentially interact with a c-fos/JunD heterodimer. Stimulation by EGF induced the binding of c-fos and JunD to this element and subsequently elevated promoter activity. In conclusion, an EGF/PKC/MAPK signal transduction pathway regulates equine glycoprotein α subunit gene expression through a distinct regulatory element(s) that lies between −2039 to −2032 of the equine glycoprotein α subunit promoter in trophoblasts and involves an AP-1 complex.