• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Physiology and Biochemistry >Destabilization of Heterologous Proteins Mediated by the GSK3β Phosphorylation Domain of the β-Catenin Protein
【24h】

Destabilization of Heterologous Proteins Mediated by the GSK3β Phosphorylation Domain of the β-Catenin Protein

机译：β-连环蛋白的GSK3β磷酸化结构域介导的异源蛋白的失稳

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background and Aims: Wnt/β-catenin signaling plays important roles in development and cellular processes. The hallmark of canonical Wnt signaling activation is the stabilization of β-catenin protein in cytoplasm and/or nucleus. The stability of β-catenin is the key to its biological functions and is controlled by the phosphorylation of its amino-terminal degradation domain. Aberrant activation of β-catenin signaling has been implicated in the development of human cancers. It has been recently suggested that GSK3βmay play an essential role in regulating global protein turnover. Here, we investigate if the GSK3β phosphorylation site-containing degradation domain of β-catenin is sufficient to destabilize heterologous proteins. Methods and Results: We engineer chimeric proteins by fusing β-catenin degradation domain at the N- and/or C-termini of the enhanced green fluorescent protein (eGFP). In both transient and stable expression experiments, the chimeric GFP proteins exhibit a significantly decreased stability, which can be effectively antagonized by lithium and Wnt1. An activating mutation in the destruction domain significantly stabilizes the fusion protein. Furthermore, GSK3 inhibitor SB-216763 effectively increases the GFP signal of the fusion protein. Conversely, the inhibition of Wnt signaling with tankyrase inhibitor XAV939 results in a decrease in GFP signal of the fusion proteins, while these small molecules have no significant effects on the mutant destruction domain-GFP fusion protein. Conclusion: Our findings strongly suggest that the β-catenin degradation domain may be sufficient to destabilize heterologous proteins in Wnt signaling-dependent manner. It is conceivable that the chimeric GFP proteins may be used as a functional reporter to measure the dynamic status of β-catenin signaling, and to identify potential anticancer drugs that target β-catenin signaling.
机译：背景和目的：Wnt /β-catenin信号传导在发育和细胞过程中起重要作用。典型的Wnt信号激活的标志是细胞质和/或细胞核中β-catenin蛋白的稳定。 β-catenin的稳定性是其生物学功能的关键，并受其氨基末端降解域的磷酸化作用控制。 β-catenin信号转导的异常激活与人类癌症的发展有关。最近已经提出，GSK3β可能在调节整体蛋白质更新中起重要作用。在这里，我们研究了含有GSK3β磷酸化位点的β-catenin降解结构域是否足以使异源蛋白不稳定。方法和结果：我们通过在增强型绿色荧光蛋白（eGFP）的N和/或C末端融合β-catenin降解域来工程化嵌合蛋白。在瞬时表达和稳定表达实验中，嵌合的GFP蛋白都表现出明显降低的稳定性，可以被锂和Wnt1有效拮抗。破坏结构域中的激活突变可显着稳定融合蛋白。此外，GSK3抑制剂SB-216763有效地增加了融合蛋白的GFP信号。相反，用tankyrase抑制剂XAV939抑制Wnt信号转导导致融合蛋白的GFP信号降低，而这些小分子对突变破坏域-GFP融合蛋白没有显着影响。结论：我们的发现强烈表明，β-catenin降解域可能足以以Wnt信号依赖的方式破坏异源蛋白的稳定性。可以想象，嵌合的GFP蛋白可以用作功能报告基因，以测量β-catenin信号的动态状态，并鉴定靶向β-catenin信号的潜在抗癌药物。

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