Regulation of G1 Cell Cycle Progression: Distinguishing the Restriction Point from a Nutrient-Sensing Cell Growth Checkpoint(s).
Regulation of G1 Cell Cycle Progression: Distinguishing the Restriction Point from a Nutrient-Sensing Cell Growth Checkpoint(s).
复制标题
DOI：
10.1177/1947601910392989
复制
发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Saqcena, Mahesh
中科院分区：
文献类型：
--
作者：
Foster, David A;Yellen, Paige;Saqcena, Mahesh
大多数促进肿瘤发生的遗传变化涉及G1细胞周期进程的失调。G1中的关键调控位点是生长因子依赖性限制点（R），细胞在此进行有丝分裂。除了生长因子依赖性的“R”，它映射到有丝分裂后约3.5小时的位点，在G1后期还有另一个检查点，它依赖于营养充足，也被称为R。然而，G1晚期的第二个位点可以在时间和遗传上与R区分开来。我们建议将晚期G1调控位点更恰当地称为“细胞生长”检查点，以将其与R区分开来。该检查点可能与酵母细胞周期检查点START具有进化关系，由mTOR（雷帕霉素的哺乳动物靶标）控制的信号调节。这篇综述总结了区分R和建议的细胞生长检查点的证据。由于这两个检查点在大多数（如果不是全部）人类癌症中失调，因此区分这两个不同的G1调节检查点对于靶向致癌信号的合理治疗策略具有重要意义。
Most genetic changes that promote tumorigenesis involve dysregulation of G1 cell cycle progression. A key regulatory site in G1 is a growth factor-dependent restriction point (R) where cells commit to mitosis. In addition to the growth factor-dependent "R," which maps to a site about 3.5 hours after mitosis, there is another checkpoint later in G1 that is dependent on nutritional sufficiency that has also been referred to as R. However, this second site in late G1 can be distinguished both temporally and genetically from R. We are proposing that the late G1 regulatory site be more appropriately referred to as a "cell growth" checkpoint to distinguish it from R. This checkpoint, which likely has an evolutionary relationship to the yeast cell cycle checkpoint START, is regulated by signals governed by mTOR, the mammalian target of rapamycin. This review summarizes evidence that distinguishes R from the proposed cell growth checkpoint. Since both checkpoints are dysregulated in most, if not all, human cancers, distinguishing between these 2 distinct G1 regulatory checkpoints has significance for rational therapeutic strategies targeting oncogenic signals.