Cyclin E ablation in the mouse
Cyclin E ablation in the mouse
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DOI：
10.1016/s0092-8674(03)00645-7
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发表时间：
2003-08-22
期刊：
影响因子：
64.5
通讯作者：
Sicinski, P
中科院分区：
文献类型：
--
作者：
Geng, Y;Yu, QY;Sicinski, P
E型细胞周期蛋白（E1和E2）被认为驱动细胞进入S期。人们普遍认为这两种E型细胞周期蛋白对于所有细胞类型的增殖都是至关重要的。在这里，我们证明了E型细胞周期蛋白在小鼠发育中基本上是必不可少的。然而，在缺乏周期蛋白e的情况下，滋养层巨细胞和巨核细胞的内复制受到严重损害。周期蛋白e缺乏的细胞在细胞连续循环的条件下积极增殖，但无法从静止的Go状态重新进入细胞周期。分子分析显示，在G(0)- >S过程中，缺乏周期蛋白E的细胞不能正常地将MCM蛋白整合到DNA复制起点。我们还发现，周期蛋白e缺陷细胞相对抵抗致癌转化。这些发现确定了E型细胞周期蛋白在细胞周期再进入中的分子功能，并揭示了细胞周期蛋白E在正常增殖和致癌增殖中的不同需求。
E type cyclins (E1 and E2) are believed to drive cell entry into the S phase. It is widely assumed that the two E type cyclins are critically required for proliferation of all cell types. Here, we demonstrate that E type cyclins are largely dispensable for mouse development. However, endoreplication of trophoblast giant cells and megakaryocytes is severely impaired in the absence of cyclin E. Cyclin E-deficient cells proliferate actively under conditions of continuous cell cycling but are unable to reenter the cell cycle from the quiescent Go state. Molecular analyses revealed that cells lacking cyclin E fail to normally incorporate MCM proteins into DNA replication origins during G(0)-->S progression. We also found that cyclin E-deficient cells are relatively resistant to oncogenic transformation. These findings define a molecular function for E type cyclins in cell cycle reentry and reveal a differential requirement for cyclin E in normal versus oncogenic proliferation.