THE ORPHAN RECEPTORS COUP-TF AND HNF-4 SERVE AS ACCESSORY FACTORS REQUIRED FOR INDUCTION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE-TRANSCRIPTION BY GLUCOCORTICOIDS
THE ORPHAN RECEPTORS COUP-TF AND HNF-4 SERVE AS ACCESSORY FACTORS REQUIRED FOR INDUCTION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE-TRANSCRIPTION BY GLUCOCORTICOIDS
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DOI：
10.1073/pnas.92.2.412
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发表时间：
1995-01-17
影响因子：
11.1
通讯作者：
GRANNER, DK
中科院分区：
文献类型：
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作者：
HALL, RK;SLADEK, FM;GRANNER, DK
糖皮质激素刺激肝磷酸烯醇式丙酮酸羧激酶（PEPCK; EC 4.1.1.32）基因表达，从而增加肝异生的速率。糖皮质激素对PEPCK基因表达的影响是由一组启动子元件介导的，这些元件统称为糖皮质激素反应单元。反应单位跨越一个100 bp的片段，包括两个糖皮质激素受体结合位点（GR 1和GR 2）和两个辅助因子结合位点（AF 1和AF 2），所有这些都是最大糖皮质激素反应所需的。AF 1元件也用作视黄酸反应元件，并且可能参与基因的发育和组织特异性表达，在这项研究中，我们报告，COUP-TF和HNF-4，两个孤儿成员的核受体超家族，结合到AF 1元件和功能作为辅助因子的糖皮质激素反应的PEPCK基因。
Glucocorticoids stimulate hepatic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) gene expression, thereby increasing the rate of gluconeogenesis. The effect of glucocorticoids on PEPCK gene expression is mediated by a set of promoter elements collectively referred to as the glucocorticoid response unit. The response unit spans a 100-bp segment and includes two glucocorticoid receptor binding sites (GR1 and GR2) and two accessory factor binding sites (AF1 and AF2), all of which are required for a maximal glucocorticoid response, The AF1 element also serves as a retinoic acid response element and may be involved in developmental and tissue-specific expression of the gene, In this study we report that COUP-TF and HNF-4, two orphan members of the nuclear receptor superfamily, bind to the AF1 element and function as accessory factors for the glucocorticoid response of the PEPCK gene.