Glucocorticoid receptor-cAMP response element-binding protein interaction and the response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids.

Glucocorticoid receptor-cAMP response element-binding protein interaction and the response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids.
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DOI:
10.1016/s0021-9258(18)53327-5
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发表时间:
1993-03
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
E. Imai;J. Miner;J. Mitchell;Keith R. Yamamoto;D. Granner
E. Imai;J. Miner;J. Mitchell;Keith R. Yamamoto;D. Granner
中科院分区:
其他
文献类型:
--
作者:
E. Imai;J. Miner;J. Mitchell;Keith R. Yamamoto;D. Granner

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磷酸烯醇式丙酮酸羧激酶(PEPCK)基因编码的限速酶在胚胎发育。糖皮质激素通过多组分调节复合物增强PEPCK基因表达。我们发现,对糖皮质激素的完全反应需要两个DNA片段:1)糖皮质激素反应单元(GRU),位于-400位点,包含两个辅助因子元件(AF 1和AF 2)和两个糖皮质激素受体结合位点(GR 1和GR 2),2)位于-90位点的基础启动子/环AMP反应元件(E/CRE),与转录因子CREB结合。GR和CREB之间在体外观察到蛋白质-蛋白质相互作用,这可能解释了E/CRE在PEPCK基因的糖皮质激素反应中的作用。
The phosphoenolpyruvate carboxykinase (PEPCK) gene encodes the rate-limiting enzyme in gluconeogenesis. Glucocorticoids enhance PEPCK gene expression through a multicomponent regulatory complex. We show that a full response to glucocorticoids requires two DNA segments: 1) a glucocorticoid response unit (GRU), centered at about position -400, which contains two accessory factor elements (AF1 and AF2) and two glucocorticoid receptor binding sites (GR1 and GR2), and 2) a basal promoter/cyclic AMP response element (E/CRE) at about position -90, which binds the transcription factor CREB. A protein-protein interaction was observed in vitro between GR and CREB that might account for the role of the E/CRE in the glucocorticoid response of the PEPCK gene.