Miskimins Robin, Srinivasan Rekha, Marin-Husstege Mireya, Miskimins W Keith, Casaccia-Bonnefil Patrizia
Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion, SD 57069, USA.
J Neurosci Res. 2002 Jan 1;67(1):100-5. doi: 10.1002/jnr.10080.
The process of oligodendrocyte differentiation is a complex event that requires cell cycle withdrawal, followed by the activation of a specific transcriptional program responsible for the synthesis of myelin genes. Because growth arrest precedes differentiation, we sought to investigate the role of cell cycle molecules in the activation of myelin gene promoters. We hypothesized that the cell cycle inhibitor p27(Kip1), which is primarily responsible for arresting proliferating oligodendrocyte progenitors, may be involved in the transcriptional regulation of myelin genes. In agreement with this hypothesis, overexpression of p27(Kip1) in the CG4 cell line, but not in 3T3 fibroblasts, enhances the expression of luciferase driven by the myelin basic protein (MBP) promoter. Interestingly, this effect is specific for p27(Kip1); overexpression of other cell cycle inhibitors had no effect. Additionally, this effect is independent of halting the cell cycle; treatment with the cell cycle blocker roscovitine did not affect MBP promoter usage. We conclude that p27(Kip1) contributes to oligodendrocyte differentiation by regulating transcription of the MBP gene.
少突胶质细胞分化过程是一个复杂的事件，需要细胞周期退出，随后激活负责髓鞘基因合成的特定转录程序。由于生长停滞先于分化，我们试图研究细胞周期分子在髓鞘基因启动子激活中的作用。我们假设，主要负责使增殖的少突胶质细胞祖细胞停滞的细胞周期抑制剂p27（Kip1）可能参与髓鞘基因的转录调控。与该假设一致，p27（Kip1）在CG4细胞系中过表达，但在3T3成纤维细胞中未过表达，增强了由髓鞘碱性蛋白（MBP）启动子驱动的荧光素酶表达。有趣的是，这种效应是p27（Kip1）特有的；其他细胞周期抑制剂的过表达没有效果。此外，这种效应与细胞周期停滞无关；用细胞周期阻滞剂roscovitine处理不影响MBP启动子的使用。我们得出结论，p27（Kip1）通过调节MBP基因的转录促进少突胶质细胞分化。
