The screening of the second‐site suppressor mutations of the common p53 mutants
The screening of the second‐site suppressor mutations of the common p53 mutants
复制标题
DOI：
10.1002/ijc.22724
复制
发表时间：
2007-08
影响因子：
6.4
通讯作者：
Kazunori Otsuka;S. Kato;Y. Kakudo;S. Mashiko;H. Shibata;C. Ishioka
中科院分区：
文献类型：
--
作者：
Kazunori Otsuka;S. Kato;Y. Kakudo;S. Mashiko;H. Shibata;C. Ishioka
通过随机诱变发现的p53第二位点抑制（SSS）突变可以恢复一些肿瘤来源的p53的失活功能。为了筛选新的SSS突变对抗常见的p53突变体，利用p53错义突变文库将基因内第二位点（SS）突变引入突变体p53 cDNA中。由此产生的具有背景和SS突变的p53突变体在酵母和人类细胞系统中恢复p53转激活功能的能力进行了检测。我们发现了12个新的SSS突变，包括H178Y与常见突变G245S的突变。令人惊讶的是，当与携带H178Y突变的p53共表达时，G245S表型被挽救。这一结果表明，基因内抑制基因突变可能以分子间方式恢复蛋白质功能。这种分子间机制可能为恢复失活的p53功能和抑制肿瘤治疗提供新的策略。©2007 Wiley‐Liss, Inc。
Second‐site suppressor (SSS) mutations in p53 found by random mutagenesis have shown to restore the inactivated function of some tumor‐derived p53. To screen novel SSS mutations against common mutant p53s, intragenic second‐site (SS) mutations were introduced into mutant p53 cDNA in a comprehensive manner by using a p53 missense mutation library. The resulting mutant p53s with background and SS mutations were assayed for their ability to restore the p53 transactivation function in both yeast and human cell systems. We identified 12 novel SSS mutations including H178Y against a common mutation G245S. Surprisingly, the G245S phenotype is rescued when coexpressed with p53 bearing the H178Y mutation. This result indicated that there is a possibility that intragenic suppressor mutations might restore the protein function in an intermolecular manner. The intermolecular mechanism may lead to novel strategies for restoring inactivated p53 function and tumor suppression in cancer treatment. © 2007 Wiley‐Liss, Inc.