Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation
Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation
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DOI：
10.1093/emboj/16.2.306
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发表时间：
1997-01-15
期刊：
影响因子：
11.4
通讯作者：
Raff, M
中科院分区：
文献类型：
--
作者：
Durand, B;Gao, FB;Raff, M
许多类型的脊椎动物前体细胞在停止和最终分化之前分裂有限的次数，在任何情况下都不知道是什么原因导致它们停止分裂，我们一直在研究增殖前体细胞产生有丝分裂后少突胶质细胞的问题，这些细胞在中枢神经系统中产生髓鞘，我们在这里展示了细胞周期控制系统的两个组成部分，细胞周期蛋白D1和Cdc2激酶，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在细胞增殖过程中逐渐积累，并在少突胶质细胞中高水平存在。我们的发现与p27的积累可能是决定前体细胞增殖何时停止和分化开始的内在计数机制的一部分，以及计数机制指示时间时阻止细胞周期的效应机制的一部分相一致。最近其他人发现p27缺陷小鼠在所有器官中都有细胞数量增加，这表明p27的这种功能并不局限于少突胶质细胞谱系。
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.