一个常见的E2F-1和p73通路介导TCR激活诱导的细胞死亡
N A Lissy1, P K Davis, M Irwin
1Howard Hughes Medical Institute, Department of Pathology, Washington University School of Medicine, St Louis Missouri 63110, USA.
Nature
|October 18, 2000
概括
激活T细胞受体会通过E2F-1和p73引发亡,而不是通过p53. 这一过程对于T细胞调节至关重要,涉及到晚期G1细胞周期检查点,突出显示p73.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 在循环的外围T细胞上激发T细胞受体 (TCR) 刺激会诱导细胞亡,称为TCR激活诱导的细胞死亡 (TCR-AICD).
- TCR-AICD独立于瘤抑制蛋白p53发生,并涉及晚期G1细胞周期检查点.
- E2F-1转录因子,一种亡诱导体,在T细胞数量中起作用,因为其破坏导致T细胞数量增加和大病.
研究的目的:
- 研究TCR激活诱导细胞死亡 (TCR-AICD) 背后的分子机制.
- 确定E2F-1和p73在TCR介导的亡中的作用.
- 为了阐明TCR-AICD所涉及的细胞周期检查点.
主要方法:
- 在接受TCR-AICD的T细胞中分析基因表达.
- 在T细胞中引入主导负蛋白 (E2F-1,p73,E2F-2,E2F-4,p53).
- 在基因零的初级T细胞 (E2F-1-null,p73-null) 中评估TCR介导的亡.
主要成果:
- 经过TCR-AICD的T细胞诱导了与p53相关的基因p73.
- 主导阴性E2F-1或p73蛋白质保护T细胞免受TCR介导的亡,而主导阴性E2F-2,E2F-4或p53则没有.
- E2F-1-null或p73-null初级T细胞没有经历TCR介导的亡.
结论:
- TCR-AICD发生在G1细胞周期晚期的检查点上,这取决于E2F-1和p73活动.
- 与p53不同,p73集成了受体介导的亡刺激.
- 这些发现揭示了调节T细胞亡的新途径.
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