A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells
A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells
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DOI：
10.1101/gad.55671
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发表时间：
2002-12-01
影响因子：
10.5
通讯作者：
McKay, RDG
中科院分区：
文献类型：
--
作者：
Tsai, RYL;McKay, RDG
干细胞自我更新的独特特性表明了调节其细胞周期进程的特定机制。在本研究中，我们鉴定了一种新的蛋白质——nucleostemin，它存在于中枢神经系统干细胞、胚胎干细胞和几种癌细胞系的核仁中，并且优先由其他富含干细胞的群体表达。它包含一个 N 端基本结构域和两个 GTP 结合基序。当干细胞分化时，在体外和体内细胞周期退出之前，nucleostemin 表达迅速降低。 nucleostemin 的消耗或过度表达会降低 CNS 干细胞和转化细胞的细胞增殖。突变分析表明，过量的 nucleostemin，特别是缺乏 GTP 调节结构域的突变体，会阻止细胞进入有丝分裂并以 p53 依赖性方式导致细胞凋亡。 N 端基本结构域指定核仁定位、p53 相互作用，并且是过度表达引起的细胞死亡所必需的。这项工作描述了一种控制中枢神经系统干细胞和癌细胞细胞周期进程的新型核仁机制。
The unique property of stem cells to self-renew suggests specific mechanisms that regulate their cell-cycle progression. In the present study, we identify a novel,protein, nucleostemin, found in the nucleoli of CNS stem cells, embryonic stem cells, and several cancer cell lines and preferentially expressed by other stem cell-enriched populations. It contains an N-terminal basic domain and two GTP-binding motifs. When stem cells differentiate, nucleostemin expression decreases rapidly prior to cell-cycle exit both in vitro and in vivo. Depletion or overexpression of nucleostemin reduces cell proliferation in CNS stem cells and transformed cells. Mutation analysis indicates that excessive nucleostemin, particularly mutants that lack the GTP-regulatory domain, prevents cells from entering mitosis and causes apoptosis in a p53-dependent manner. The N-terminal basic domain specifies nucleolar localization, the p53 interaction, and is required for the cell death caused by overexpression. This work describes a novel nucleolar mechanism that controls the cell-cycle progression in CNS stem cells and cancer cells.