Geldanamycin induces G2 arrest in U87MG glioblastoma cells through downregulation of Cdc2 and cyclin B1
Geldanamycin induces G2 arrest in U87MG glioblastoma cells through downregulation of Cdc2 and cyclin B1
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DOI：
10.1016/j.bcp.2007.01.022
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发表时间：
2007-05-15
影响因子：
5.8
通讯作者：
Zagzag, David
中科院分区：
文献类型：
--
作者：
Nomura, Naoko;Nomura, Motohiro;Zagzag, David
细胞周期进程需要精确表达和激活几个细胞周期蛋白和细胞周期蛋白依赖性激酶。格尔德霉素（GA）影响各种细胞的细胞周期进程。我们分析了GA诱导的胶质母细胞瘤细胞的细胞周期调控。GA以细胞系依赖性方式诱导胶质母细胞瘤细胞G2或M期阻滞。GA可降低U87MG细胞Cdc 2和cyclin B1的表达。GA处理的细胞中磷酸化Cdc 2与Cdc 2一起沿着下降。该细胞系在GA处理后显示G2阻滞。相反，GA不能下调U251MG细胞中这些细胞周期调节因子。在U251MG细胞中，GA除使细胞周期阻滞于G2期外，还使细胞周期阻滞于M期。接下来，我们分析了GA诱导调节U87 MG细胞中Cdc 2和cyclin B1的机制。Cdc 2和cyclin B1被GA泛素化。MG132消除GA诱导的Cdc2和细胞周期蛋白B1的减少，表明这些蛋白质被蛋白酶体降解。总之，GA控制Cdc2和细胞周期蛋白B1在胶质母细胞瘤细胞中的稳定性是种依赖性的。Cdc 2和cyclin B1可能是胶质母细胞瘤细胞对GA反应不同的原因。(c)2007爱思唯尔公司All rights reserved.
Cell cycle progression requires precise expression and activation of several cyclins and cyclin-dependent kinases. Geldanamycin (GA) affects cell cycle progression in various kinds of cells. We analyzed GA-induced cell cycle regulation in glioblastoma cells. GA-induced G2 or M arrest in glioblastoma cells in a cell line-dependent manner. GA decreased the expression of Cdc2 and cyclin B1 in U87MG cells. And phosphorylated Cdc2 decreased along with Cdc2 in the GA-treated cells. This cell line showed G2 arrest after GA treatment. in contrast, GA failed to down-regulate these cell cycle regulators in U251MG cells. In U251MG cells, the cell cycle was arrested at M phase in addition to G2 by GA. Next, we analyzed the mechanism of the GA-induced regulation of Cdc2 and cyclin B1 in U87MG cells. Cdc2 and cyclin B1 were ubiquitinated by GA. MG132 abrogated the GA-induced decrease of Cdc2 and cyclin B1 indicating that these proteins were degraded by proteasomes. In conclusion, GA controls the stability of Cdc2 and cyclin B1 in glioblastomas cell species-dependently. Cdc2 and cyclin B1 might be responsible for the different responses of glioblastoma cell lines to GA. (c) 2007 Elsevier Inc. All rights reserved.