Ectopic expression of p27Kip1 in oligodendrocyte progenitor cells results in cell-cycle growth arrest

被引:0
|
作者
Tikoo, R
Osterhout, DJ
Casaccia-Bonnefil, P
Seth, P
Koff, A
Chao, MV
机构
[1] NYU, Med Ctr, Skirball Inst, Mol Neurobiol Program, New York, NY 10016 USA
[2] Cornell Univ Med Coll, Dept Neurol & Neurosci, New York, NY 10012 USA
[3] NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA
来源
JOURNAL OF NEUROBIOLOGY | 1998年 / 36卷 / 03期
关键词
oligodendrocyte; differentiation; cell cycle; cyclin-dependent kinase;
D O I
10.1002/(SICI)1097-4695(19980905)36:3<431::AID-NEU10>3.0.CO;2-E
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Oligodendrocyte differentiation is a complex process believed to be controlled by an intrinsic mechanism associated with cell-cycle arrest. Recently, the cell-cycle inhibitor protein p27(Kip1) has been proposed as a key element in causing growth arrest of oligodendrocyte precursor cells. To investigate the effects of p27 upon oligodendrocyte cell development, we have introduced the p27 cDNA in oligodendrocyte progenitor cells using an adenovirus vector. Progenitor cells normally express low levels of p27, After adenoviral infection and p27 overexpression, progenitor cells were able to undergo cell-cycle arrest, even in the presence of strong mitogens. The effects of p27 were shown to be directly upon cyclin-dependent kinase-2 (CDK2), the protein kinase complex responsible for G1/S transition, as immunodepletion of oligodendrocyte extracts of p27 protein resulted in the activation of CDK2 activity, However, cells that became growth arrested owing to infection with p27 adenovirus did not display conventional oligodendrocyte differentiation markers, such as O4 or O1, Taken together, these data provide mechanistic evidence indicating that p27 is primarily involved in oligodendroglial progenitor proliferation by inhibiting CDK2 activity and inducing oligodendrocyte cell-cycle arrest. (C) 1998 John Wiley & Sons, Inc.
引用
收藏
页码:431 / 440
页数:10
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