E2f1-3从祖细胞中的激活剂转换为分化细胞中的抑制剂
Jean-Leon Chong1, Pamela L Wenzel, M Teresa Sáenz-Robles
1Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Nature
|December 18, 2009
概括
视网母细胞瘤蛋白 (Rb) 和E2f激活剂 (E2f1-3) 在细胞循环控制中具有双重作用. E2f1-3对原始细胞生存至关重要,而不是分裂,并抑制分化.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 视网膜母细胞瘤蛋白 (Rb) 传统上通过隔离E2f激活剂 (E2f1-3) 来抑制细胞循环的进展.
- E2f1-3被认为是驱动细胞进入S阶段和增殖的关键因子.
研究的目的:
- 研究E2f1,E2f2和E2f3在哺乳动物细胞周期控制中的体内功能.
- 澄清E2f1-3作为激活剂与抑制剂的取决于上下文的作用.
主要方法:
- 使用了组织特异性创转基因小鼠和条件E2f等位基因.
- 在小鼠胚胎干细胞,胚胎和小肠中检查了E2f1-3三重缺陷.
主要成果:
- 在分裂的原始细胞中,E2f1-3充当激活剂,但对于分裂是不可或缺的,对生存至关重要.
- 在分化细胞中,E2f1-3与Rb复合,抑制E2f标并促进细胞周期的退出.
- 在分化细胞中的Rb无活化将E2f1-3切换为激活器,导致异胎分裂;E2f1-3损失挽救了这一点.
结论:
- E2f1-3根据细胞环境 (分裂与分化) 动态地作为激活剂或抑制剂起作用.
- E2f1-3对原始细胞生存至关重要,并在分化过程中细胞周期退出中发挥关键作用.
- 这项研究重新定义了E2f1-3在正常和异常细胞周期中的作用,影响了癌症研究.
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