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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Eradication of pathogenic β-catenin by Skp1/Cullin/ F box ubiquitination machinery
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Eradication of pathogenic β-catenin by Skp1/Cullin/ F box ubiquitination machinery

机译：Skp1 / Cullin / F盒泛素化机制消除病原性β-catenin

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摘要

The use of Skp1/Cull 1/F box (SCF) ubiquitin-conjugation machinery as a potential knockout tool offers a means of eradicating disease-causing proteins. Here a chimeric F box protein (CFP) was engineered to achieve selective eradication of pathogenic β-catenin in colorectal cancer. We show that CFP specifically searches for and subsequently links the abnormal β-catenin to the cellular SCF ubiquitination complex. Introduction of the CFP to colorectal cancer cells induced targeted ubiquitination and proteolytic degradation of nuclear and cytoplasmic free β-catenin while preserving its normal cellular adhesion counterpart. Elimination of pathogenic β-catenin suppressed constitutive Wingless/Wnt signaling and inhibited in vitro and in vivo tumor cell growth. This study demonstrates a practical utility of a SCF-based knockout system as a tool in targeting an abnormal protein that affects growth and transformation.
机译：使用Skp1 / Cull 1 / F盒（SCF）泛素结合机器作为潜在的敲除工具，可以消除引起疾病的蛋白质。在这里，嵌合F盒蛋白（CFP）被工程化以实现在大肠癌中选择性清除病原性β-连环蛋白。我们显示CFP专门搜索并随后将异常β-catenin链接到细胞SCF泛素化复合体。将CFP引入大肠癌细胞可诱导核蛋白和细胞质游离β-catenin的靶向泛素化和蛋白水解降解，同时保留其正常的细胞粘附对应物。消除病原性β-catenin可抑制组成性Wingless / Wnt信号传导并抑制体外和体内肿瘤细胞的生长。这项研究证明了基于SCF的敲除系统作为靶向影响生长和转化的异常蛋白质的工具的实用性。

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