p27(Kip1) enhances myelin basic protein gene promoter activity.
p27(Kip1) enhances myelin basic protein gene promoter activity.
复制标题
p27(Kip1)增强髓磷脂碱性蛋白基因启动子活性。
DOI：
10.1002/jnr.10080
复制
发表时间：
2002
影响因子：
4.2
通讯作者：
Casaccia-Bonnefil,Patrizia
中科院分区：
文献类型：
--
作者：
Miskimins,Robin;Srinivasan,Rekha;Marin-Husstege,Mireya;Miskimins,WKeith;Casaccia-Bonnefil,Patrizia
少突胶质细胞分化的过程是一个复杂的事件，需要细胞周期退出，然后激活负责合成髓磷脂基因的特定转录程序。由于生长停滞先于分化，我们试图研究细胞周期分子在髓磷脂基因启动子激活中的作用。我们假设细胞周期抑制剂 p27Kip1 主要负责阻止少突胶质细胞祖细胞的增殖，可能参与髓磷脂基因的转录调节。与这一假设一致，p27Kip1 在 CG4 细胞系中的过表达（但在 3T3 成纤维细胞中则不然）增强了由髓磷脂碱性蛋白 (MBP) 启动子驱动的荧光素酶的表达。有趣的是，这种效应是 p27Kip1 所特有的；其他细胞周期抑制剂的过度表达没有效果。此外，这种效应与细胞周期的停止无关。细胞周期阻滞剂 roscovitine 治疗不影响 MBP 启动子的使用。我们得出结论，p27Kip1 通过调节 MBP 基因的转录来促进少突胶质细胞分化。 © 2002 Wiley-Liss, Inc.
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 p27Kip1, 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 p27Kip1in 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 p27Kip1; 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 p27Kip1contributes to oligodendrocyte differentiation by regulating transcription of the MBP gene. © 2002 Wiley‐Liss, Inc.