...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >CASZ1 inhibits cell cycle progression in neuroblastoma by restoring pRb activity
【24h】

CASZ1 inhibits cell cycle progression in neuroblastoma by restoring pRb activity

机译：CASZ1通过恢复pRb活性抑制神经母细胞瘤的细胞周期进程

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Dysregulation of cell cycle genes such as Cyclin D1 and Chk1 contributes to the undifferentiated phenotype of neuroblastoma (NB). CAS Z1 functions as a tumor suppressor in NB; here we sought to determine how loss of the CAS Z1 contributes to cell cycle dysregulation in NB. CAS Z1 restoration in NB cells delays NB cell cycle progression. The earliest changes occurred within 8 h of CAS Z1 restoration in SY5Y cells with a 2.8-fold increase in the level of p21, an inhibitor of Cdk2/4. By 16 h, there was a 40% decrease in the steady-state levels of Cdk6. Restoration of CAS Z1 decreases Cdk2- dependent cyclins A and E protein levels and Cdk4/6-dependent Cyclin D1 protein levels. The restoration of CAS Z1 resulted in a decrease in pRb phosphorylation and a significant reduction of E2F transcriptional activity. Subsequent to the changes in the G1/S transition, induction of CAS Z1 results in a decrease in Cyclin B levels and Cdc25c phosphatase levels, an upstream activator of the G 2/M regulator CyclinB:Cdk1. In addition, induction of CAS Z1 results in a decrease in the levels of phospho-Chk1, a key M-phase regulatory kinase. Similar results were found in a NB cell line with MYCN amplification. Taken together, this study indicates that restoration of CAS Z1 activates pRb in G1 and inhibits the G2/M regulators Cyclin B1 and Chk1, leading to a lengthening of NB cell cycle progression and a subsequent decrease in cell proliferation.
机译：细胞周期基因如细胞周期蛋白D1和Chk1的失调有助于神经母细胞瘤（NB）的未分化表型。 CAS Z1在NB中起抑癌作用。在这里，我们试图确定CAS Z1的丢失如何导致NB细胞周期失调。 NB细胞中的CAS Z1恢复会延迟NB细胞周期进程。最早的变化发生在SY5Y细胞中CAS Z1恢复的8小时内，p21（Cdk2 / 4的抑制剂）的水平增加了2.8倍。到16小时，Cdk6的稳态水平降低了40％。恢复CAS Z1会降低Cdk2依赖性细胞周期蛋白A和E的蛋白水平以及Cdk4 / 6依赖性细胞周期蛋白D1的蛋白水平。 CAS Z1的恢复导致pRb磷酸化的减少和E2F转录活性的显着降低。在G1 / S过渡的变化之后，CAS Z1的诱导导致Cyclin B水平和Cdc25c磷酸酶水平降低，这是G 2 / M调节剂CyclinB：Cdk1的上游激活剂。此外，CAS Z1的诱导导致磷酸化Chk1（一种关键的M期调节激酶）水平降低。在具有MYCN扩增的NB细胞系中发现了相似的结果。两者合计，这项研究表明，CAS Z1的恢复激活了G1中的pRb，并抑制了G2 / M调节剂Cyclin B1和Chk1，从而导致NB细胞周期进程的延长和随后细胞增殖的减少。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号