首页> 外文期刊>Cellular Signalling >Major vault protein regulates cell growth/survival signaling through oxidative modifications
【24h】

Major vault protein regulates cell growth/survival signaling through oxidative modifications

机译:主要穹顶蛋白通过氧化修饰调节细胞生长/存活信号

获取原文
获取原文并翻译 | 示例
           

摘要

Major vault protein forms a hollow, barrel-like structure in the cell called the vault, whose functions and regulation are not well understood. The present study reports that major vault protein regulates growth/survival signaling in human airway smooth muscle cells through oxidative modifications. The promotion of protein S-glutathionylation by asthma mediators such as interleukin-22 and platelet-derived growth factor or by knocking down glutaredoxin-1 or thioredoxin activated cell growth signaling. Mass spectrometry identified that major vault protein is glutathionylated. Major vault protein knockdown enhanced cell death and inhibited STAT3 and Akt signaling. We identified a protein partner of major vault protein that is regulated by glutaredoxin-1, namely myosin-9, which was found to serve as a cell death factor. Knocking down myosin-9 or promoting protein S-glutathionylation by knocking down glutaredoxin-1 inhibited the death of airway smooth muscle cells by heating to simulate bronchial thermoplasty, a clinically successful procedure for the treatment of severe asthma. These results establish a novel signaling pathway in which ligand/receptor-mediated oxidation promotes the S-glutathionylation of major vault protein, which in turn binds to myosin-9 to suppress the heat-inginduced death of airway smooth muscle cells. (C) 2015 Elsevier Inc. All rights reserved.
机译:主要穹ault蛋白在称为穹ault的细胞中形成空心的桶状结构,其功能和调控尚不十分清楚。本研究报告主要穹v蛋白通过氧化修饰调节人气道平滑肌细胞的生长/存活信号。哮喘介体(如白介素22和血小板衍生的生长因子)或通过敲低glutaredoxin-1或硫氧还蛋白激活的细胞生长信号来促进蛋白S-谷胱甘肽化。质谱鉴定出主要穹ault蛋白被谷胱甘肽化。大型穹顶蛋白敲低可增加细胞死亡并抑制STAT3和Akt信号转导。我们鉴定出了主要的穹顶蛋白的蛋白伴侣,该蛋白伴侣受到了谷胱甘肽-1(即肌球蛋白-9)的调节,而谷胱甘肽-1被认为是细胞死亡因子。通过敲低glutaredoxin-1敲低myosin-9或促进蛋白S-谷胱甘肽酰化可通过加热模拟支气管热成形来抑制气道平滑肌细胞的死亡,这是治疗严重哮喘的临床成功方法。这些结果建立了一条新的信号通路,其中配体/受体介导的氧化促进了主要穹顶蛋白的S-谷胱甘肽酰化,后者又与肌球蛋白9结合,抑制了热诱导的气道平滑肌细胞死亡。 (C)2015 Elsevier Inc.保留所有权利。

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