Structure of human MDM2 complexed with RPL11 reveals the molecular basis of p53 activation

文献类型： 外文期刊

第一作者： Zheng, Jiangge

作者： Zheng, Jiangge;Lang, Yue;Zhang, Qi;Cui, Di;Sun, Haili;Jiang, Lun;Chen, Zhenhang;Zhang, Rui;Gao, Yina;Wu, Wei;Tang, Jun;Chen, Zhongzhou;Lang, Yue;Cui, Di;Sun, Haili;Zhang, Rui;Tang, Jun;Tian, Wenli

作者机构：

关键词： Cancer;Complex structure;Molecular basis;p53 activation;RPL11—MDM2

期刊名称：GENES & DEVELOPMENT （ 影响因子：11.361； 五年影响因子：12.029 ）

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年卷期：

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收录情况： SCI

摘要： The central region of MDM2 is critical for p53 activation and tumor suppression. Upon ribosomal stress, this region is bound by ribosomal proteins, particularly ribosomal protein L11 (RPL11), leading to MDM2 inactivation and subsequent p53 activation. Here, we solved the complex structure of human MDM2-RPL11 at 2.4 ?. MDM2 extensively interacts with RPL11 through an acidic domain and two zinc fingers. Formation of the MDM2-RPL11 complex induces substantial conformational changes in both proteins. RPL11, unable to bind MDM2 mutants, fails to induce the activation of p53 in cells. MDM2 mimics 28S rRNA binding to RPL11. The C4 zinc finger determines RPL11 binding to MDM2 but not its homolog, MDMX. Our results highlight the essential role of the RPL11-MDM2 interaction in p53 activation and tumor suppression and provide a structural basis for potential new anti-tumor drug development.

分类号： R394

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