...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of cellular biochemistry. >Heat Shock Protein 90 Regulates Subcellular Localization of Smads in Mv1Lu Cells
【24h】

Heat Shock Protein 90 Regulates Subcellular Localization of Smads in Mv1Lu Cells

机译：热激蛋白90调节Mv1Lu细胞中Smads的亚细胞定位。

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

Heat shock protein 90 (HSP90) regulates the stability of various proteins and plays an essential role in cellular homeostasis. Many client proteins of HSP90 are involved in cell growth, survival, and migration; processes that are generally accepted as participants in tumorigenesis. HSP90 is also up-regulated in certain tumors. Indeed, the inhibition of HSP90 is known to be effective in cancer treatment. Recently, studies showed that HSP90 regulates transforming growth factor beta 1(TGF-beta 1)-induced transcription by increasing the stability of the TGF-beta receptor. TGF-beta signaling also has been implicated in cancer, suggesting the possibility that TGF-beta 1 and HSP90 function cooperatively during the cancer cell progression. Here in this paper, we investigated the role of HSP90 in TGF-beta 1-stimulated Mv1Lu cells. Treatment of Mv1Lu cells with the HSP90 inhibitor, 17-allylamino-demethoxy-geldanamycin (17AAG), or transfection with truncated HSP90 (Delta HSP90) significantly reduced TGF-beta 1-induced cell migration. Pretreatment with 17AAG or transfection with Delta HSP90 also reduced the levels of phosphorylated Smad2 and Smad3. In addition, the HSP90 inhibition interfered the nuclear localization of Smads induced by constitutively active Smad2 (S2EE) or Smad3 (S3EE). We also found that the HSP90 inhibition decreased the protein level of importin-beta 1 which is known to regulate R-Smad nuclear translocation. These data clearly demonstrate a novel function of HSP90; HSP90 modulates TGF-beta signaling by regulating Smads localization. Overall, our data could provide a detailed mechanism linking HSP90 and TGF-beta signaling. The extension of our understanding of HSP90 would offer a better strategy for treating cancer. (C) 2015 Wiley Periodicals, Inc.
机译：热休克蛋白90（HSP90）调节各种蛋白的稳定性，并在细胞体内平衡中发挥重要作用。 HSP90的许多客户蛋白都参与细胞的生长，存活和迁移。通常被认为是肿瘤发生过程的过程。 HSP90在某些肿瘤中也上调。实际上，已知抑制HSP90在癌症治疗中是有效的。最近，研究表明HSP90通过增加TGF-β受体的稳定性来调节转化生长因子β1（TGF-β1）诱导的转录。 TGF-β信号转导也与癌症有关，提示在癌细胞发展过程中TGF-β1和HSP90协同起作用的可能性。在本文中，我们研究了HSP90在TGF-β1刺激的Mv1Lu细胞中的作用。用HSP90抑制剂，17-烯丙基氨基-脱甲氧基-格尔德霉素（17AAG）或用截短的HSP90（Delta HSP90）转染来治疗Mv1Lu细胞，可显着降低TGF-β1诱导的细胞迁移。 17AAG预处理或Delta HSP90转染也降低了磷酸化Smad2和Smad3的水平。此外，HSP90抑制作用会干扰由组成型活性Smad2（S2EE）或Smad3（S3EE）诱导的Smads的核定位。我们还发现，HSP90抑制作用降低了Importin-beta 1的蛋白水平，而后者已知可调节R-Smad核易位。这些数据清楚地证明了HSP90的新功能。 HSP90通过调节Smads定位来调节TGF-β信号传导。总的来说，我们的数据可以提供链接HSP90和TGF-beta信号的详细机制。扩展我们对HSP90的了解将为治疗癌症提供更好的策略。 （C）2015威利期刊公司

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