...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Cell Growth Inhibition by Farnesyltransferase Inhibitors Is Mediated by Gain of Geranylgeranylated RhoB
【24h】

Cell Growth Inhibition by Farnesyltransferase Inhibitors Is Mediated by Gain of Geranylgeranylated RhoB

机译：法尼基转移酶抑制剂对细胞生长的抑制作用是由香叶基香叶基化的RhoB的介导的

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Recent results have shown that the ability of farnesyltransferase inhibitors (FTIs) to inhibit malignant cell transformation and Ras prenylation can be separated. We proposed previously that farnesylated Rho proteins are important targets for alternation by FTIs, based on studies of RhoB (the FTI-Rho hypothesis). Cells treated with FTIs exhibit a loss of farnesylated RhoB but a gain of geranylgeranylated RhoB (RhoB-GG), which is associated with loss of growth-promoting activity. In this study, we tested whether the gain of RhoB-GG elicited by FTI treatment was sufficient to mediate FTI-induced cell growth inhibition. In support of this hypothesis, when expressed in Ras-transformed cells RhoB-GG induced phenotypic reversion, cell growth inhibition, and activation of the cell cycle kinase inhibitor p21WAF1. RhoB-GG did not affect the phenotype or growth of normal cells. These effects were similar to FTI treatment insofar as they were all induced in transformed cells but not in normal cells. RhoB-GG did not promote anoikis of Ras-transformed cells, implying that this response to FTIs involves loss-of-function effects. Our findings corroborate the FTI-Rho hypothesis and demonstrate that gain-of-function effects on Rho are part of the drug mechanism. Gain of RhoB-GG may explain how FTIs inhibit the growth of human tumor cells that lack Ras mutations.
机译：最近的结果表明，法尼基转移酶抑制剂（FTI）抑制恶性细胞转化和Ras异戊二烯化的能力可以分开。基于RhoB（FTI-Rho假设）的研究，我们先前提出法尼基化Rho蛋白是FTI替代的重要靶标。用FTI处理的细胞显示法尼基化RhoB缺失，但香叶基香叶基化RhoB（RhoB-GG）获得，这与促进生长的活性降低有关。在这项研究中，我们测试了FTI处理引起的RhoB-GG的增益是否足以介导FTI诱导的细胞生长抑制。为支持该假设，当在Ras转化细胞中表达时，RhoB-GG诱导表型逆转，细胞生长抑制和细胞周期激酶抑制剂p21WAF1的激活。 RhoB-GG不影响正常细胞的表型或生长。这些作用与FTI处理相似，因为它们都是在转化细胞中诱导的，而不是在正常细胞中诱导的。 RhoB-GG不能促进Ras转化细胞的失范，这表明对FTI的这种反应涉及功能丧失的影响。我们的发现证实了FTI-Rho假说，并证明对Rho的功能获得作用是药物机制的一部分。 RhoB-GG的获得可能解释了FTI如何抑制缺乏Ras突变的人类肿瘤细胞的生长。

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