Coats S, Flanagan W M, Nourse J, Roberts J M
Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Science. 1996 May 10;272(5263):877-80. doi: 10.1126/science.272.5263.877.
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 G1 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 p27Kip1. This was correlated with inactivation of essential G1 cyclin-CDK complexes and with cell cycle arrest in G1. 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.
缺乏血清促有丝分裂原的细胞要么立即进入细胞周期停滞，要么完成有丝分裂并在下一个细胞周期停滞。从依赖促有丝分裂原到不依赖促有丝分裂原的转变发生在细胞周期的G1期中期到后期，这一转变被称为限制点。缺乏血清促有丝分裂原的小鼠Balb/c - 3T3成纤维细胞积累了细胞周期蛋白依赖性激酶（CDK）抑制剂p27Kip1。这与必需的G1期细胞周期蛋白 - CDK复合物的失活以及G1期的细胞周期停滞相关。特定促有丝分裂原允许细胞通过限制点的能力与其下调p27的能力平行，并且p27表达的反义抑制可防止因促有丝分裂原耗竭而导致的细胞周期停滞。因此，p27是在限制点将促有丝分裂信号与细胞周期连接起来的信号通路的重要组成部分。
