Ubiquitination-resistant p53 protein transduction therapy facilitates anti-cancer effect on the growth of human malignant glioma cells
Ubiquitination-resistant p53 protein transduction therapy facilitates anti-cancer effect on the growth of human malignant glioma cells
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DOI：
10.1016/j.febslet.2005.06.021
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发表时间：
2005-07-18
期刊：
影响因子：
3.5
通讯作者：
Matsui, H
中科院分区：
文献类型：
--
作者：
Michiue, H;Tomizawa, K;Matsui, H
使用聚精氨酸的蛋白转导疗法可以将具有生物活性的 p53 蛋白递送到癌细胞中并抑制细胞的增殖。然而，这种疗法的一个缺点是所递送的蛋白质的细胞内半衰期短。在这里，我们生成了突变蛋白，其中 C 末端的多个赖氨酸残基被精氨酸取代。突变蛋白在神经胶质瘤细胞中有效传递，并且对 Mdm2 介导的泛素化具有抵抗力。此外，突变蛋白表现出更高的转录调节活性和对神经胶质瘤细胞增殖的强大抑制作用。这些结果表明，泛素化抗性p53蛋白疗法可能成为一种新的有效癌症疗法。 (c) 2005 年由 Elsevier B.V. 代表欧洲生化学会联合会出版。
Protein transduction therapy using poly-arginine can deliver the bioactive p53 protein into cancer cells and inhibits the proliferation of the cells. However, one disadvantage of such therapy is the short intracellular half-life of the delivered protein. Here, we generated mutant proteins in which multiple lysine residues in the C-terminal were substituted by arginines. The mutant proteins were effectively delivered in glioma cells and were resistant to Mdm2-mediated ubiquitination. Moreover, the mutant proteins displayed higher transcription regulatory activity and powerful inhibition of the proliferation of glioma cells. These results suggest that ubiquitination-resistant p53 protein therapy may become a new effective cancer therapy. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.