The EGF response element in the prolactin promoter.
The EGF response element in the prolactin promoter.
复制标题
催乳素启动子中的 EGF 反应元件。
DOI：
10.1016/s0303-7207(99)00043-x
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发表时间：
1999
影响因子：
4.1
通讯作者：
Stanley,FM
中科院分区：
文献类型：
--
作者：
Jacob,KK;Wininger,E;DiMinni,K;Stanley,FM
表皮生长因子（EGF）增加GH4细胞中催乳素基因的表达，但这种反应所需的启动子元件尚未明确定义。我们使用催乳素启动子的缺失和接头扫描突变体，在大鼠近端启动子中鉴定了一个对EGF信号传导至关重要的二分元件-96/-87，-76/-67。当转移到异源启动子（乳腺肿瘤病毒）时，该元件在正常或反向方向上都有活性。我们以前已经确定了这个元件作为cAMP/胰岛素反应元件的催乳素启动子。然而，EGF的作用与对胰岛素或cAMP的反应是相加的，这意味着EGF通过不同于胰岛素或cAMP的机制激活催乳素基因转录。催乳素启动子的EGF反应元件是Ets相关转录因子家族的识别序列，并且Ets相关因子已显示结合该元件。c-Ets-1的DNA结合结构域的表达作为Ets相关转录因子的显性负性抑制剂，可使GH4细胞中EGF增加的催乳素-CAT表达降低65%。因此，EGF和胰岛素都可以通过Ets相关的转录因子发出信号，以激活催乳素基因在催乳素近端启动子中的相同反应元件处的转录。
Epidermal growth factor (EGF) increases prolactin gene expression in GH4 cells, but the promoter element(s) required for this response has not been clearly defined. We identified a bipartite element −96/−87, −76/−67 in the rat proximal promoter that is essential for EGF signaling using deletion and linker-scanning mutants of the prolactin promoter. This element was active in either normal or inverted orientation when transferred to a heterologous promoter (mammary-tumor virus). We had previously identified this element as the cAMP/insulin response element of the prolactin promoter. However, the effects of EGF are additive with the responses to insulin or cAMP implying that EGF activated prolactin gene transcription by a mechanism different from insulin or cAMP. The EGF response element of the prolactin promoter is a recognition sequence for the Ets-related family of transcription factors and Ets-related factors have been shown to bind this element. Expression of the DNA-binding domain of c-Ets-1, which acts as a dominant negative inhibitor of Ets-related transcription factors, reduces EGF-increased prolactin–CAT expression 65% in GH4 cells. Thus, both EGF and insulin may signal through Ets-related transcription factors to activate prolactin gene transcription at the same response element in the prolactin proximal promoter.