Estrogen regulation of the insulin-like growth factor I gene transcription involves an AP-1 enhancer.
Estrogen regulation of the insulin-like growth factor I gene transcription involves an AP-1 enhancer.
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发表时间：
1994-06
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通讯作者：
Y. Umayahara;R. Kawamori;H. Watada;E. Imano;N. Iwama;T. Morishima;Y. Yamasaki;Y. Kajimoto;T. Kamada
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作者：
Y. Umayahara;R. Kawamori;H. Watada;E. Imano;N. Iwama;T. Morishima;Y. Yamasaki;Y. Kajimoto;T. Kamada
为了进一步阐明胰岛素样生长因子- i （IGF-I）在调节雌激素作用中的生理作用，我们试图确定这一现象的分子基础。在表达外源性雌激素受体（ER）的HepG2细胞中，含有鸡IGF-I启动子600碱基对的报告基因质粒在10(-6)m17 β -雌二醇的作用下使荧光素酶的表达增加8.6倍，表明IGF-I启动子是雌激素调控的靶点。虽然在启动子片段中没有发现传统的雌激素应答元件，但AP-1基序被证明是必不可少的；通过翻译后修饰，Fos-Jun与AP-1基序结合的雌激素响应性增强介导了雌激素的作用。雌激素- er复合物和Fos-Jun复合物之间的直接或间接相互作用似乎促进了Fos-Jun与目标DNA的结合。虽然内质网与靶DNA的结合不被认为参与了信号通路，但DNA结合结构域缺陷的内质网并没有介导这一现象，这为内质网DNA结合结构域在促进某些蛋白质-蛋白质相互作用方面的独特功能的存在提供了支持。总之，我们目前的观察结果表明，鸡IGF-I基因启动子是由雌激素通过一个独特的途径控制的，涉及Fos、Jun和ER的DNA结合域。
As a step toward elucidating the physiological role of insulin-like growth factor-I (IGF-I) in mediating estrogen action, we sought to determine the molecular basis of the phenomenon. In HepG2 cells expressing exogenous estrogen receptors (ER), a reporter gene plasmid containing 600 base pairs of the chicken IGF-I promoter enhanced expression of luciferase 8.6-fold in response to 10(-6) M 17 beta-estradiol, indicating that the IGF-I promoter is a target of estrogen regulation. Although no conventional estrogen-responsive element was identified within the promoter fragment, the AP-1 motif located therein was shown to be essential; the estrogen-responsive enhancement of the Fos-Jun binding to the AP-1 motif, which takes place by means of post-translational modification, mediates the estrogen action. A direct or indirect interaction between the estrogen-ER complex and the Fos-Jun complex seems to facilitate the Fos-Jun binding to the target DNA. Although ER binding to the target DNA was not considered to be involved in the signaling pathway, the DNA binding domain-deficient ER did not mediate the phenomenon, providing support for the existence of a unique function of the DNA binding domain of ER in facilitating some protein-protein interaction. In conclusion, our present observations demonstrate that the chicken IGF-I gene promoter is controlled by estrogen through a unique pathway involving Fos, Jun, and the DNA binding domain of ER.