A Protein Biosynthesis Machinery Strategy for Identifying P53PTC-Rescuing Compounds as Synergic Anti-Tumor Drugs
A Protein Biosynthesis Machinery Strategy for Identifying P53PTC-Rescuing Compounds as Synergic Anti-Tumor Drugs
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识别 P53PTC 救援化合物作为协同抗肿瘤药物的蛋白质生物合成机制策略
DOI：
10.1002/slct.201802635
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发表时间：
2018-10-24
期刊：
影响因子：
2.1
通讯作者：
Su, Zhengding
中科院分区：
文献类型：
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作者：
Zhou, Jingjing;Qiu, Chengbin;Su, Zhengding
过早终止密码子 (PTC) 的通读是治疗 PTC 引起的疾病的一种有前途的策略。在癌症中，p53 的抗肿瘤活性常常因形成过早终止的 p53 蛋白 (p53(PTC)) 而失效。目前尚缺乏p53(PTC)救援药物。在此，我们设计了一种可行的策略，利用大肠杆菌细胞和肺癌 H1299 细胞中的蛋白质生物合成机制来识别 p53PTC 救援化合物，这两种细胞都含有 p53(PTC)-GFP 融合蛋白表达盒。拯救的 p53(PTC) 蛋白启用了 GFP 标签，用于荧光光谱测量。我们的数据显示，氨基糖苷类G418不仅能有效拯救H1299细胞中的p53（PTC），还能协同增强抗肿瘤药物阿霉素的疗效。我们的工作深入了解了用于癌症治疗的 p53(PTC) 救援药物的发现。
The readthrough of premature termination codons (PTCs) is a promising strategy for curing PTC-causing diseases. In cancers, the p53 anti-tumor activity is often disabled by forming premature terminated p53 protein (p53(PTC)). Currently, there are lack of p53(PTC)-rescuing drugs. Herein we designed a feasible strategy for identifying p53PTC-rescuing compounds using protein biosynthesis machinery in E. coli cells and the lung cancer H1299 cells both harboring p53(PTC)-GFP fusion protein expression cassettes. Rescued p53(PTC) protein enabled a GFP-tag for fluorescence spectroscopic measurements. Our data revealed that the aminoglycoside G418 not only efficiently rescued p53(PTC) in H1299 cells, but also synergistically enhanced the efficacy of antitumor drug doxorubicin. Our work gave an insight into the discovery of p53(PTC)-rescuing drugs for cancer therapy.