A Designed Peptide Targets Two Types of Modifications of p53 with Anti-cancer Activity

文献类型： 外文期刊

第一作者： Liang, Lunxi

作者： Liang, Lunxi;Wang, Huanbin;Yao, Han;Li, Chushu;Zhang, Yao;Wang, Jilin;Wang, Yingchao;Zhao, Shuliang;Qian, Jin;Chen, Yingxuan;Fang, Jing-Yuan;Xu, Jie;Shi, Hubing;Xiang, Dabin;Shi, Hubing;Xiang, Dabin;Shi, Hubing;Xiang, Dabin;Li, Zhaoli;Bu, Zhigao;Song, Ningning;Hu, Ye;Xu, Qi;Ma, Yanlei;Cheng, Zhongyi

作者机构：

期刊名称：CELL CHEMICAL BIOLOGY （ 影响因子：8.116； 五年影响因子：8.838 ）

ISSN： 2451-9448

年卷期： 2018 年 25 卷 6 期

页码：

收录情况： SCI

摘要： Many cancer-related proteins are controlled by composite post-translational modifications (PTMs), but prevalent strategies only target one type of modification. Here we describe a designed peptide that controls two types of modifications of the p53 tumor suppressor, based on the discovery of a protein complex that suppresses p53 (suppresome). We found that Morn3, a cancer-testis antigen, recruits different PTM enzymes, such as sirtuin deacetylase and ubiquitin ligase, to confer composite modifications on p53. The molecular functions of Morn3 were validated through in vivo assays and chemico-biological intervention. A rationally designed Morn3-targeting peptide (Morncide) successfully activated p53 and suppressed tumor growth. These findings shed light on the regulation of protein PTMs and present a strategy for targeting two modifications with one molecule.

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