FUNCTIONAL ANTAGONISM BETWEEN ONCOPROTEIN C-JUN AND THE GLUCOCORTICOID RECEPTOR
FUNCTIONAL ANTAGONISM BETWEEN ONCOPROTEIN C-JUN AND THE GLUCOCORTICOID RECEPTOR
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DOI：
10.1016/0092-8674(90)90397-w
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发表时间：
1990-09-21
期刊：
影响因子：
64.5
通讯作者：
EVANS, RM
中科院分区：
文献类型：
--
作者：
SCHULE, R;RANGARAJAN, P;EVANS, RM
我们提出证据表明糖皮质激素受体(GR)和转录因子JUN/AP-1可以通过一种不依赖于DNA结合的新机制相互抑制S的转录激活。C-jun的过表达可以阻止糖皮质激素诱导的携带功能性糖皮质激素反应元件(GRE)的基因的激活。隐蔽地，GR能够抑制AP-1介导的转录激活。突变分析表明，GR的配体结合结构域和DNA结合结构域以及包括c-jun的亮氨酸拉链在内的区域都是进行抑制所必需的。凝胶滞留分析表明，细菌表达的c-jun破坏了GR-GRE复合体。这些数据表明，两个不同类别的转录因子的成员可以通过一种可能涉及蛋白质-蛋白质相互作用的机制来对抗彼此的S活性。
We present evidence that the glucocorticoid receptor (GR) and transcription factor Jun/AP-1 can reciprocally repress one another''s transcriptional activation by a novel mechanism that is independent of DNA binding. Overexpression of c-Jun prevents the glucocorticoid-induced activation of genes carrying a functional glucocorticoid response element (GRE). Coversely, GR is able to repress AP-1-mediated transcriptional activation. Mutant analysis reveals that the ligand binding and DNA binding domains of GR and the region including the leucine zipper of c-Jun are required for repression. Gel retardation analysis demonstrates that bacterially expressed c-Jun disrupts GR-GRE complexes. These data indicate that members of two distinct classes of transcription factors can oppose one another''s activity through a mechanism likely involving protein-protein interactions.