Cooperative effects of genes controlling the G(2)/M checkpoint.
Cooperative effects of genes controlling the G(2)/M checkpoint.
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DOI：
10.1101/gad.14.13.1584
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发表时间：
2000-07
影响因子：
10.5
通讯作者：
Timothy A. Chan;Paul M. Hwang;H. Hermeking;K. Kinzler;B. Vogelstein
中科院分区：
文献类型：
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作者：
Timothy A. Chan;Paul M. Hwang;H. Hermeking;K. Kinzler;B. Vogelstein
据信，多个效应物独立地控制允许细胞周期阶段之间的转换的检查点。然而，这还没有在哺乳动物细胞中得到严格证明。p53诱导的基因p21和14-3-3sigma都是G（2）阻滞所必需的，并允许对这一基本原则进行特异性测试。我们产生了p21和14-3-3sigma缺陷的人类细胞，并确定双敲除是否比单敲除对DNA损伤更敏感。p21（-/-）14-3-3sigma（-/-）细胞对DNA损伤或p53的外源性表达比仅缺乏p21或仅缺乏14-3-3sigma的细胞显著更敏感。因此，p21和14-3-3sigma在G（2）/M检查点中发挥不同但互补的作用，并有助于解释为什么生长停滞途径节点的基因，如p53，是癌细胞突变的靶点。
It is believed that multiple effectors independently control the checkpoints permitting transitions between cell cycle phases. However, this has not been rigorously demonstrated in mammalian cells. The p53-induced genes p21 and 14-3-3sigma are each required for the G(2) arrest and allow a specific test of this fundamental tenet. We generated human cells deficient in both p21 and 14-3-3sigma and determined whether the double knockout was more sensitive to DNA damage than either single knockout. p21(-/-) 14-3-3sigma(-/-) cells were significantly more sensitive to DNA damage or to the exogenous expression of p53 than cells lacking only p21 or only 14-3-3sigma. Thus, p21 and 14-3-3sigma play distinct but complementary roles in the G(2)/M checkpoint, and help explain why genes at the nodal points of growth arrest pathways, like p53, are the targets of mutation in cancer cells.