...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nuclear IKK activity leads to dysregulated Notch-dependent gene expression in colorectal cancer
【24h】

Nuclear IKK activity leads to dysregulated Notch-dependent gene expression in colorectal cancer

机译：核IKK活性导致结直肠癌中Notch依赖的基因表达失调

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

Nuclear functions for I kappa B kinase (IKK), including phosphorylation of histone H3 and nuclear corepressors, have been recently described. Here, we show that IKK is activated in colorectal tumors concomitant with the presence of phosphorylated SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor that is aberrantly localized in the cytoplasm. In these tumors, IKK alpha associates to the chromatin of specific Notch targets, leading to the release of SMRT. Abrogation of IKK activity by BAY11-7082 or by expressing dominant negative IKK alpha restores the association of SMRT with Notch target genes, resulting in specific gene repression. Finally, BAY11-7082 significantly reduces tumor size in colorectal cancer xenografts (CRC-Xs) implanted in nude mice.
机译：最近已经描述了IκB激酶（IKK）的核功能，包括组蛋白H3的磷酸化和核共表达。在这里，我们显示IKK在大肠肿瘤中被激活，并伴有磷酸化的SMRT（视黄酸和甲状腺激素受体的沉默介导子）共表达体的异常定位在细胞质中。在这些肿瘤中，IKKα与特定的Notch靶标的染色质缔合，导致SMRT释放。 BAY11-7082或通过表达显性负IKKα废除IKK活性可恢复SMRT与Notch靶基因的结合，从而导致特异性基因抑制。最后，BAY11-7082大大减少了裸鼠体内移植的结直肠癌异种移植物（CRC-Xs）中的肿瘤大小。

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