NF-AT组件定义了一个针对T细胞激活的转录因子家族
1Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University Medical School, California 94305.
Nature
|June 9, 1994
概括
研究人员确定了NF-AT转录复合体的两个组成部分,NF-ATp和NF-ATc. NF-ATc对于T细胞中介素-2 (IL-2) 基因表达至关重要,并通过不同的信号通路进行调节.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 细胞信号传递 细胞信号传递
背景情况:
- 激活T细胞的核因子 (NF-AT) 转录复合体对于协调免疫反应至关重要.
- 了解NF-AT的组成部分和调节对于破译免疫细胞功能至关重要.
研究的目的:
- 为了净化和描述NF-AT转录复合物的单个组成部分.
- 阐明NF-AT成分在基因调节中的作用,特别是介质蛋白-2 (IL-2) 表达的作用.
- 研究调节NF-AT功能的信号通路.
主要方法:
- 两种不同的蛋白质的净化,代表NF-AT的先前存在的 (NF-ATp) 和细胞质 (NF-ATc) 组成部分.
- 在非T淋巴细胞中表达全长NF-ATc互补DNA.
- 在T淋巴细胞中使用主导负的NF-ATc结构.
- 对NF-ATcRNA表达模式的分析.
- 研究细胞内Ca2+和蛋白激酶C激活对NF-ATc的影响.
主要成果:
- 两个蛋白质NF-ATp和NF-ATc被净化为NF-AT复合物的组成部分.
- NF-ATc表达激活非T细胞中的IL-2促进体;主导负NF-ATc阻断T细胞中的IL-2促进体激活,证实NF-ATc在IL-2基因表达中的作用.
- NF-ATc RNA表达主要发生在淋巴细胞组织中,并由T细胞激活诱导.
- NF-ATp与Dorsal/Rel家族共享同源性,并且具有更广泛的组织分布.
- 涉及细胞内Ca2+和蛋白激酶C的独特信号通路汇聚在NF-ATc上,调节其功能.
结论:
- NF-ATc是IL-2基因表达的关键调节者,对T细胞激活至关重要.
- NF-ATc功能由不同的细胞内信号级联调节,突出显示了免疫反应调节的融合点.
- NF-ATp和NF-ATc的差异表达和特征表明NF-ATc复合体内的特殊作用.
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