Durand B, Gao F B, Raff M
MRC Laboratory for Molecular Cell Biology and the Biology Department, University College London, UK.
EMBO J. 1997 Jan 15;16(2):306-17. doi: 10.1093/emboj/16.2.306.
Many types of vertebrate precursor cells divide a limited number of times before they stop and terminally differentiate. In no case is it known what causes them to stop dividing. We have been studying this problem in the proliferating precursor cells that give rise to postmitotic oligodendrocytes, the cells that make myelin in the central nervous system. We show here that two components of the cell cycle control system, cyclin D1 and the Cdc2 kinase, are present in the proliferating precursor cells but not in differentiated oligodendrocytes, suggesting that the control system is dismantled in the oligodendrocytes. More importantly, we show that the cyclin-dependent kinase (Cdk) inhibitor p27 progressively accumulates in the precursor cells as they proliferate and is present at high levels in oligodendrocytes. Our findings are consistent with the possibility that the accumulation of p27 is part of both the intrinsic counting mechanism that determines when precursor cell proliferation stops and differentiation begins and the effector mechanism that arrests the cell cycle when the counting mechanism indicates it is time. The recent findings of others that p27-deficient mice have an increased number of cells in all of the organs examined suggest that this function of p27 is not restricted to the oligodendrocyte cell lineage.
许多类型的脊椎动物前体细胞在停止分裂并终末分化之前只能分裂有限的次数。目前尚不清楚是什么导致它们停止分裂。我们一直在对产生有丝分裂后少突胶质细胞（即中枢神经系统中形成髓鞘的细胞）的增殖前体细胞进行研究。我们在此表明，细胞周期控制系统的两个组分，即细胞周期蛋白D1和Cdc2激酶，存在于增殖前体细胞中，但不存在于分化的少突胶质细胞中，这表明该控制系统在少突胶质细胞中被拆解。更重要的是，我们发现细胞周期蛋白依赖性激酶（Cdk）抑制剂p27在前体细胞增殖时逐渐积累，并在少突胶质细胞中高水平存在。我们的研究结果与以下可能性一致：p27的积累既是决定前体细胞何时停止增殖并开始分化的内在计数机制的一部分，也是当计数机制表明时机已到便使细胞周期停滞的效应机制的一部分。其他人最近的研究发现，p27基因缺陷型小鼠在所有检查的器官中细胞数量均增加，这表明p27的这种功能并不局限于少突胶质细胞谱系。
