• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>other >Knockdown of μ-calpain in Fanconi Anemia FA-A cells by siRNA Restores αII Spectrin levels and Corrects Chromosomal Instability and Defective DNA Interstrand Cross-link Repair
【2h】

Knockdown of μ-calpain in Fanconi Anemia FA-A cells by siRNA Restores αII Spectrin levels and Corrects Chromosomal Instability and Defective DNA Interstrand Cross-link Repair

机译：通过siRNa还原αII血影蛋白的水平并校正染色体不稳定和有缺陷的DNa链间交联修复在范可尼贫血Fa-a细胞敲低μ-钙蛋白酶

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

We have previously shown that there is a deficiency in the structural protein, nonerythroid α spectrin (αIISp), in cells from patients with Fanconi anemia (FA). These studies indicate that this deficiency is due to reduced stability of αIISp and correlates with decreased repair of DNA interstrand cross-links and chromosomal instability in FA cells. An important factor in the stability of αIISp is its susceptibility to cleavage by the protease, μ-calpain. We hypothesized that increased μ-calpain cleavage of αIISp in FA cells leads to increased breakdown of αIISp and that knocking-down expression of μ-calpain in FA cells should restore levels of αIISp and correct a number of the phenotypic defects observed. The results showed that there is increased μ-calpain activity in FA-A, FA-C, FA-D2, FA-F and FA-G cells which could account for the deficiency in αIISp in these FA cells. Protein interaction studies indicated that FANCA and FANCG bind directly to μ-calpain. We hypothesize that this binding may lead to inhibition of μ-calpain activity in normal cells. Knocking-down μ-calpain by siRNA in FA-A cells restored levels of αIISp to normal and reversed a number of the cellular deficiencies in these cells. It corrected the DNA repair defect and the chromosomal instability observed after exposure to a DNA interstrand cross-linking agent. These studies indicated that FA proteins may play an important role in maintaining stability of αIISp in the cell by regulating its cleavage by μ-calpain. Thus by reducing breakdown of αIISp in FA cells, it may be possible to reverse a number of the cellular deficiencies observed in this disorder.

著录项

相似文献

  • 外文文献
  • 中文文献
代理获取

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