A phorbol ester response element within the human T-cell receptor beta-chain enhancer.
A phorbol ester response element within the human T-cell receptor beta-chain enhancer.
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人类 T 细胞受体 β 链增强剂内的佛波酯反应元件。
DOI：
10.1073/pnas.89.20.9934
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发表时间：
1992
影响因子：
11.1
通讯作者：
Owen,MJ
中科院分区：
文献类型：
--
作者：
Prosser,HM;Wotton,D;Gegonne,A;Ghysdael,J;Wang,S;Speck,NA;Owen,MJ
在T细胞活化期间，蛋白激酶C途径的活化剂增加了T细胞受体β链基因增强子的活性。突变增强子构建体的分析鉴定了赋予佛波酯诱导的两个元件β E2和β E3。多聚化β E2作为佛波酯反应元件单独起作用。β E2和β E3都含有一个共有的Ets结合位点，可以直接与c-ets-1原癌基因的产物结合。这两个区域还结合了第二个因子，核心结合因子。β E2 Ets位点的突变消除了β E2多聚体的诱导。β E2和β E3 Ets位点突变也深刻地影响增强子的活性和诱导。相比之下，增强子活性，但不是其诱导的β E2核心结合因子位点的突变的影响。共转染研究表明，Ets-1特异性抑制多聚化β E2元件和完整的T细胞受体β链增强子的活性。这些数据表明，T细胞受体β链增强子响应蛋白激酶C介导的激活信号，通过一个功能域，由两个元素组成，其中包含Ets转录因子的结合位点，这是负调控的Ets-1。
The activity of the T-cell receptor beta-chain gene enhancer is increased by activators of the protein kinase C pathway during T-cell activation. Analysis of mutant enhancer constructs identified two elements, beta E2 and beta E3, conferring phorbol ester inducibility. Multimerized beta E2 acted in isolation as a phorbol ester-responsive element. Both beta E2 and beta E3, which contain a consensus Ets-binding site, were shown to bind directly to the product of the c-ets-1 protooncogene. Both regions also bound a second factor, core-binding factor. Mutation of the beta E2 Ets site abolished the inducibility of the beta E2 multimer. beta E2 and beta E3 Ets site mutations also profoundly affected activity and inducibility of the enhancer. In contrast, enhancer activity but not its inducibility was affected by mutation of the beta E2 core-binding factor site. Cotransfection studies showed that Ets-1 specifically repressed activity of the multimerized beta E2 element and the complete T-cell receptor beta-chain enhancer. These data show that the T-cell receptor beta-chain enhancer responds to protein kinase C-mediated activation signals via a functional domain, composed of two elements, which contains binding sites for Ets transcription factors and which is negatively regulated by Ets-1.