...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The FEBS journal >Downregulated adaptor protein p66Shc mitigatesautophagy process by low nutrient and enhancesapoptotic resistance in human lung adenocarcinoma A549cells
【24h】

Downregulated adaptor protein p66Shc mitigatesautophagy process by low nutrient and enhancesapoptotic resistance in human lung adenocarcinoma A549cells

机译：下调的衔接蛋白p66Shc通过低营养来缓解自噬过程并增强人肺腺癌A549细胞的凋亡抗性

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

Macroautophagy or autophagy is a lysosome-dependent process in whichenzymatic degradation and recycling of cytosolic components occur instressful contexts. The mechanisms underlying the signaling from starvationto the regulation of autophagy are not fully understood. We previouslyshowed that the Src family member p66Shc (focal adhesion-associated66 kDa isoform of the Src homology and collagen) promotes anoikis andsuppresses tumor metastasis via k-Ras-dependent control of proliferationand survival. However, the role of p66Shc in low-nutrient-induced autophagy-related pathways remains elusive. In this work, human lung adenocarcinomaA549 cells were used to further investigate the biological effectsof p66Shc on autophagy and apoptotic resistance. Here, we show that deficiencyof p66Shc mitigates the low-nutrient-induced autophagy process inthe levels of microtubule-associated protein 1A light chain protein 3B(LC3B) conversion, in the number of autophagic vacuoles and in p62/sequestosome1 protein degradation. However, autophagy-related proteinBeclin 1 was not significantly changed during low-nutrient treatment. Furthermore,we found that prolonged phosphorylation of extracellular signaling-regulated kinase (Erk)1/2, but not phosphorylation of Akt issignificantly sustained when p66Shc expression is inhibited by shRNA. Inaddition, cleavage of caspase 7 and poly(ADP-ribose) polymerase, but notcaspase 6 and 9 are retarded with this effect compared to the shRNA controlcells. Together, these findings suggest the possibility that p66Shc playsa pivotal role in coordinately regulating autophagy process and apoptoticresistance in A549 cells under nutrient-limited conditions.
机译：巨自噬或自噬是溶酶体依赖的过程，其中酶降解和胞质组分的循环发生在紧张的环境中。从饥饿到自噬调节的信号转导机制尚不完全清楚。我们以前显示，Src家族成员p66Shc（Src同源性和胶原的局部粘着相关的66 kDa异构体）可促进神经过敏，并通过k-Ras依赖性增殖和存活控制来抑制肿瘤转移。然而，p66Shc在低营养诱导的自噬相关途径中的作用仍然难以捉摸。在这项工作中，人类肺腺癌A549细胞用于进一步研究p66Shc对自噬和凋亡抗性的生物学作用。在这里，我们显示p66Shc的缺乏减轻了微管相关蛋白1A轻链蛋白3B（LC3B）转化水平，自噬泡的数量和p62 / sequestosome1蛋白降解中低养分诱导的自噬过程。但是，自噬相关蛋白Beclin 1在低营养处理期间没有明显改变。此外，我们发现当shRNA抑制p66Shc的表达时，胞外信号调节激酶（Erk）1/2的磷酸化延长，而Akt的磷酸化则不能显着维持。另外，与shRNA对照细胞相比，胱天蛋白酶7和聚（ADP-核糖）聚合酶，但非胱天蛋白酶6和9的切割被延迟，具有这种作用。在一起，这些发现表明在营养有限的条件下，p66Shc在协调调节A549细胞的自噬过程和凋亡抗性中起关键作用。

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