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人白细胞介素2受体γ链基因启动子的功能分析

Functional analysis of the human interleukin 2 receptor gamma chain gene promoter.

作者信息

Ohbo K, Takasawa N, Ishii N, Tanaka N, Nakamura M, Sugamura K

机构信息

Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan.

出版信息

J Biol Chem. 1995 Mar 31;270(13):7479-86. doi: 10.1074/jbc.270.13.7479.

Abstract

The third component of the interleukin (IL) 2 receptor, gamma chain, is essential not only for IL-2- but also for IL-4-, IL-7-, IL-9-, and IL-15-induced proliferation of lymphocytes. To elucidate the mechanisms by which the gamma chain is expressed, we have analyzed the promoter region of the gamma chain gene. The 633-base pair fragment upstream of the initiation codon showed the promoter activity in human hematopoietic cell lines, Jurkat and THP-1, when linked to the luciferase gene. With a series of 5'-deletion mutants, the basal promoter activity was found in a fragment from nucleotide 80 to 58 upstream from the RNA start site, including an Ets binding sequence. Treatment of cells with either 12-O-tetradecanoylphorbol-13-acetate or phytohemagglutinin but not forskolin induced transcription from the gamma chain gene promoter. A viral trans-acting transcriptional activator, Tax, of human T-cell leukemia virus type I elevated expression of the gamma chain gene. In contrast, IL-2 decreased transcription from the IL-2 receptor gamma chain promoter. These results suggest that expression of the gamma chain is regulated at the transcription level by extracellular stimuli and may be implicated in immune response.

摘要

白细胞介素(IL)-2受体的第三个组成部分——γ链,不仅对IL-2诱导的淋巴细胞增殖至关重要,对IL-4、IL-7、IL-9和IL-15诱导的淋巴细胞增殖也必不可少。为了阐明γ链表达的机制,我们分析了γ链基因的启动子区域。起始密码子上游633个碱基对的片段与荧光素酶基因相连时,在人造血细胞系Jurkat和THP-1中显示出启动子活性。通过一系列5'-缺失突变体,发现基础启动子活性存在于RNA起始位点上游核苷酸80至58的片段中,该片段包含一个Ets结合序列。用12-O-十四酰佛波醇-13-乙酸酯或植物血凝素处理细胞可诱导γ链基因启动子转录,但用福斯高林处理则不能。人T细胞白血病病毒I型的病毒反式作用转录激活因子Tax可提高γ链基因的表达。相反,IL-2可降低IL-2受体γ链启动子的转录。这些结果表明,γ链的表达在转录水平受细胞外刺激调节,可能与免疫反应有关。

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