Requirement of p27(Kip1) for restriction point control of the fibroblast cell cycle
Requirement of p27(Kip1) for restriction point control of the fibroblast cell cycle
复制标题
DOI：
10.1126/science.272.5263.877
复制
发表时间：
1996-05-10
期刊：
影响因子：
56.9
通讯作者：
Roberts, JM
中科院分区：
文献类型：
--
作者：
Coats, S;Flanagan, WM;Roberts, JM
缺乏血清有丝分裂原的细胞在下一个细胞周期中要么立即发生细胞周期停滞，要么完全有丝分裂和停滞。从有丝分裂原依赖到有丝分裂原非依赖性的转变发生在细胞周期的G(1)中后期，称为限制点。去除血清丝裂原的小鼠Balb/c-3T3成纤维细胞积聚了细胞周期蛋白依赖性激酶(CDK)抑制物p27(Kip1)。这与G(1)细胞周期蛋白-CDK复合体失活和细胞周期停滞有关。特定的有丝分裂原允许通过限制点的能力与它们下调p27的能力是平行的，反义抑制p27表达可以阻止细胞周期停滞对有丝分裂原耗尽的反应。因此，p27是连接有丝分裂信号和细胞周期在限制点的重要组成部分。
Cells deprived of serum mitogens will either undergo immediate cell cycle arrest or complete mitosis and arrest in the next cell cycle. The transition from mitogen dependence to mitogen independence occurs in the mid- to late G(1) phase of the cell cycle and is called the restriction point. Murine Balb/c-3T3 fibroblasts deprived of serum mitogens accumulated the cyclin-dependent kinase (CDK) inhibitor p27(Kip1). This was correlated with inactivation of essential G(1) cyclin-CDK complexes and with cell cycle arrest in G(1). The ability of specific mitogens to allow transit through the restriction point paralleled their ability to down-regulate p27, and antisense inhibition of p27 expression prevented cell cycle arrest in response to mitogen depletion. Therefore, p27 is an essential component of the pathway that connects mitogenic signals to the cell cycle at the restriction point.