...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Use of Recombinant Cell-Permeable Small Peptides To Modulate Glucocorticoid Sensitivity of Acute Lymphoblastic Leukemia Cells
【24h】

Use of Recombinant Cell-Permeable Small Peptides To Modulate Glucocorticoid Sensitivity of Acute Lymphoblastic Leukemia Cells

机译：使用重组细胞可渗透的小肽来调节急性淋巴细胞白血病细胞的糖皮质激素敏感性

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

Glucocorticoid (GC) hormones induce apoptosis in T-cell and pre-B-cell acute lymphoblastic leukemia (ALL) cells. Steroid-mediated apoptosis requires a threshold level of the glucocorticoid receptor ( GR) protein, and increasing the intracellular GR levels in ALL cells would augment their hormone sensitivity. A protein transduction domain (PTD) approach was used to accomplish this. We produced an HIV Tat PTD domain fusion protein (Tat-GR_(554-777) that potentially competes for the degradation of GR protein by the ubiquitin-proteasome system and should thus increase its intracellular levels by "stabilizing" the GR. We also designed a fusion peptide for the c-Myb DNA binding domain, Tat-c-Myb DBD, since the biological function of this peptide as a dominant negative inhibitor of the c-Myb protein was already known. Purified, bacterially expresssed Tat-c-Myb DBD and Tat-CR_(.554-777) exhibited highly efficient transduction into cultured ALL cell lines including 697 (pre-B-ALL) and CEM-C7 (T-ALL) cells. As expected. the transduced Tat-c-Myb DBD peptide inhibited steroid-mediated stimulation of a GR promoter-luciferase reporter gene. Significantly, transduced Tat-GR554-77 effectively increased intracellular GR levels in the GC-resistant T-ALL cell line. CEM-C I , and in the pre-B-ALL 697 cell line. Furthermore, transduction of Cat-CR_(554-777) rendered GC-resistant CEM-C I cells sensitive to steroid killing and further sensitized 697 cells to steroid. The use of Tat-fusion peptide transduction may eventually lead to innovative therapeutic modalities to improve the clinical response of patients suffering from T-cell and pre-B-cell acute lymphoblastic leukemia by increasing steroid responsiveness and perhaps converting steroidresistant leukemia to a hormone-responsive phenotype.
机译：糖皮质激素（GC）激素诱导T细胞和B-Cemet急性淋巴细胞白血病（全部）细胞的细胞凋亡。类固醇介导的细胞凋亡需要糖皮质激素受体（GR）蛋白的阈值水平，并增加所有细胞中的细胞内GR水平会增加其激素敏感性。使用蛋白质转导域（PTD）方法来实现这一点。我们生产了HIV TAT PTD结构域融合蛋白（TAT-GR_（554-777），可能竞争遍突蛋白 - 蛋白酶体系的GR蛋白的降解，因此应该通过“稳定”GR来增加其细胞内水平。我们还设计了用于C-MYB DNA结合结构域的融合肽，TAT-C-MYB DBD，因为该肽作为C-MYB蛋白的显性负抑制剂的生物学功能已经已知。纯化，细菌表达的TAT-C-MYB DBD和TAT-CR _（。554-777）表现出高效的转导，进入培养的所有细胞系，包括697（B-BLI）和CEM-C7（T-All）细胞。如预期的那样。转导的TAT-C-MYB DBD肽抑制类固醇介导的GR启动子 - 荧光素酶报告基因的刺激。显着，转导的TAT-GR554-77有效地增加了GC抗性T-all细胞系中的细胞内遗传群。CEM-C I，以及预先B-所有697个细胞系。此外，CAT-CR_（554-777）的转导呈现GC抗性CEM -C I细胞对类固醇杀死和进一步敏感的697个细胞至类固醇。使用TAT-融合肽转导的使用可能最终导致创新的治疗方式，以通过提高类固醇反应性来改善患有T细胞和B-Code急性淋巴细胞白血病患者的临床响应，也许将甾体细胞白血病转化为激素响应性表型。

著录项

  • 来源
    《Biochemistry》 |2010年第41期|共10页
  • 作者

    Chuan-dong Geng; Wayne V. Vedeckis;

  • 作者单位

    Department of Biochemistry and Molecular Biology and Stanley .5. Scott Cancer Center Louisiana Slate University Health Sciences Center New Orleans. Louisiana 70112;

    Department of Biochemistry and Molecular Biology and Stanley .5. Scott Cancer Center Louisiana Slate University Health Sciences Center New Orleans. Louisiana 70112;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    GC; ALL; PTD;

    机译：GC;全部;PTD;

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