...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cancer Cell >The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein.
【24h】

The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein.

机译：通过BCR / ABL调节的SET蛋白的抑制活性，抑癌PP2A在爆炸危机CML中功能失活。

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

The oncogenic BCR/ABL kinase activity induces and maintains chronic myelogenous leukemia (CML). We show here that, in BCR/ABL-transformed cells and CML blast crisis (CML-BC) progenitors, the phosphatase activity of the tumor suppressor PP2A is inhibited by the BCR/ABL-induced expression of the PP2A inhibitor SET. In imatinib-sensitive and -resistant (T315I included) BCR/ABL+ cell lines and CML-BC progenitors, molecular and/or pharmacological activation of PP2A promotes dephosphorylation of key regulators of cell proliferation and survival, suppresses BCR/ABL activity, and induces BCR/ABL degradation. Furthermore, PP2A activation results in growth suppression, enhanced apoptosis, restored differentiation, impaired clonogenic potential, and decreased in vivo leukemogenesis of imatinib-sensitive and -resistant BCR/ABL+ cells. Thus, functional inactivation of PP2A is essential for BCR/ABL leukemogenesis and, perhaps, required for blastic transformation.
机译：致癌的BCR / ABL激酶活性诱导并维持慢性粒细胞性白血病（CML）。我们在这里显示，在BCR / ABL转化的细胞和CML blast危机（CML-BC）祖细胞中，肿瘤抑制因子PP2A的磷酸酶活性受到BCR / ABL诱导的PP2A抑制剂SET表达的抑制。在伊马替尼敏感性和耐药性（包括T315I）的BCR / ABL +细胞系和CML-BC祖细胞中，PP2A的分子和/或药理学激活可促进细胞增殖和存活的关键调节剂的去磷酸化，抑制BCR / ABL活性，并诱导BCR / ABL退化。此外，PP2A激活导致伊马替尼敏感和耐药的BCR / ABL +细胞的生长受到抑制，细胞凋亡增强，分化恢复，克隆能力减弱以及体内白血病发生率降低。因此，PP2A的功能失活对于BCR / ABL白血病的发生是必不可少的，并且可能是转化所必需的。

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