...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >The Ras Signaling Inhibitor LOX-PP Interacts with Hsp70 and c-Raf To Reduce Erk Activation and Transformed Phenotype of Breast Cancer Cells
【24h】

The Ras Signaling Inhibitor LOX-PP Interacts with Hsp70 and c-Raf To Reduce Erk Activation and Transformed Phenotype of Breast Cancer Cells

机译：Ras信号抑制剂LOX-PP与Hsp70和c-Raf相互作用，以减少乳腺癌细胞的Erk活化和转化表型

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

摘要

The lysyl oxidase gene (LOX) inhibits Ras signaling in transformed fibroblasts and breast cancer cells. Its activity was mapped to the 162-amino-acid propeptide domain (LOX-PP) of the lysyl oxidase precursor protein. LOX-PP inhibits Erk signaling, motility, and tumor formation in a breast cancer xenograft model; however, its mechanism of action is largely unknown. Here, a copurification-mass spectrometry approach was taken using ectopically expressed LOX-PP in HEK293T cells and the heat shock/chaperone protein Hsp70 identified. Hsp70 interaction with LOX-PP was confirmed using coimmunoprecipitation of intracellularly and bacterially expressed and endogenous proteins. The interaction was mapped to the Hsp70 peptide-binding domain and to LOX-PP amino acids 26 to 100. LOX-PP association reduced Hsp70 chaperone activities of protein refolding and survival after heat shock. LOX-PP interacted with the Hsp70 chaperoned protein c-Raf. With the use of ectopic expression of LOX-PP wild-type and deletion proteins, small interfering RNA (siRNA) knockdown, and Lox?/? mouse embryo fibroblasts, LOX-PP interaction with c-Raf was shown to decrease downstream activation of MEK and NF-κB, migration, and anchorage-independent growth and reduce its mitochondrial localization. Thus, the interaction of LOX-PP with Hsp70 and c-Raf inhibits a critical intermediate in Ras-induced MEK signaling and plays an important role in the function of this tumor suppressor.
机译：赖氨酰氧化酶基因（ LOX ）抑制转化的成纤维细胞和乳腺癌细胞中的Ras信号传导。其活性被映射到赖氨酰氧化酶前体蛋白的162个氨基酸的前肽域（LOX-PP）。 LOX-PP在乳腺癌异种移植模型中抑制Erk信号传导，运动性和肿瘤形成。然而，其作用机理在很大程度上尚不清楚。在这里，使用异位表达的LOX-PP在HEK293T细胞中进行了共纯化质谱法，并鉴定了热激/伴侣蛋白Hsp70。 Hsp70与LOX-PP的相互作用已通过细胞内和细菌表达以及内源性蛋白质的共免疫沉淀得到了证实。相互作用被映射到Hsp70肽结合域和LOX-PP氨基酸26到100。LOX-PP结合降低了热休克后Hsp70伴侣蛋白的蛋白折叠活性和存活率。 LOX-PP与Hsp70伴侣蛋白c-Raf相互作用。使用异位表达的LOX-PP野生型和缺失蛋白，小干扰RNA（siRNA）敲低和 Lox ？/？小鼠胚胎成纤维细胞LOX- PP与c-Raf的相互作用可减少MEK和NF-κB的下游活化，迁移和锚定非依赖性生长并降低其线粒体定位。因此，LOX-PP与Hsp70和c-Raf的相互作用抑制了Ras诱导的MEK信号传导中的关键中间体，并在该肿瘤抑制子的功能中起重要作用。

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