ROLE OF ETS1 IN LYMPHOID CELLS

ETS 1是一种转录因子，能够与富含嘌呤的核心结合 基序（-GGAA-）存在于许多细胞基因的启动子/增强子中。 ETS 1基因表达在胸腺细胞晚期被诱导 分化 ETS 1基因在静息T细胞中高水平表达， 细胞和T细胞活化后的水平非常低，这表明， ETS 1可以调节T细胞活化过程中诱导的基因。 阐明 参与ETS 1在T细胞中功能的分子机制，正义， ETS 1的反义和变体形式（缺乏DNA结合结构域的ETS 1， ETS 1 DNA结合结构域及其突变形式）异位表达 Jurkat T细胞 具有外源反义核酸的Jurkat T细胞转染子 ETS 1阻断ETS 1蛋白的形成，并产生更高水平的 与正义ETS 1和反义ETS 2转染子相比。 在反义ETS 1转染子中IL-2的产生与对照组相比呈负相关。 与再诱导的ETS 1水平有关。 IL-2启动子连接到一个 CAT报告基因在反义转染子中具有高活性， 这表明IL-2产生的增加似乎是由于转录水平的增加， 诱导 正义ETS 1和ETS 2 DNA结合域蛋白的表达 减少白细胞介素-2的形成，进一步支持了我们的观点， ETS 1负调控IL-2基因表达。 实验 正在研究ETS 1在转录和转录过程中的作用， 淋巴因子基因的转录后诱导和其他ets 目标基因。

ETS1 is a transcription factor capable of binding to purine rich core motif (-GGAA-) present in the promoter/enhancers of many cellular genes. The ETS1 gene expression is induced during late stages of thymocyte differentiation. ETS1 gene is expressed at high levels in resting T- cells and at very low levels after T-cell activation, suggesting that the ETS1 may regulate genes induced during T-cell activation. To elucidate the molecular mechanisms involved in ETS1 function in T-cells, sense, antisense and variant forms of ETS1 (ETS1 lacking DNA binding domain, ETS1 DNA binding domain and their mutant forms) are ectopically expressed in Jurkat T-cells. Jurkat T-cell transfectants with exogenous antisense ETS1 block the formation of ETS1 protein and produces higher levels of interleukin-2 compared to sense ETS1 and antisense ETS2 transfectants. The production of IL-2 in antisense ETS1 transfectants is inversely related to the levels of reinduced ETS1. The IL-2 promoter linked to a CAT reporter gene has high activity in antisense transfectants, suggesting increased IL-2 production appears to be due to transcriptional induction. Expression of sense ETS1 and ETS2 DNA binding domain protein reduces the formation of interleukin-2, further supporting our notion that the ETS1 negatively regulates IL-2 gene expression. Experiments are in progress to investigate the role of ETS1 in the transcriptional and post-transcriptional induction of lymphokine genes and in other ets target genes.