泛素
德隆
生物
蛋白质水解
计算生物学
癌变
遗传学
泛素连接酶
癌症
细胞生物学
生物化学
基因
酶
作者
Francisco Martínez-Jiménez,Ferran Muiños,Erika López‐Arribillaga,Núria López‐Bigas,Abel González-Pérez
出处
期刊:Nature cancer
[Springer Nature]
日期:2019-12-02
卷期号:1 (1): 122-135
被引量:36
标识
DOI:10.1038/s43018-019-0001-2
摘要
E3 ligases and degrons, the sequences they recognize in target proteins, are key parts of the ubiquitin-mediated proteolysis system. There are several examples of alterations of these two components of the system that have a role in cancer. Here we uncover the landscape of the contribution of such alterations to tumorigenesis across cancer types. We first systematically identified new instances of degrons across the human proteome by using a random forest classifier and validated the functionality of a dozen of them, exploiting somatic mutations across >7,000 tumors. We detected signals of positive selection across known and new degron instances. Our results reveal that several oncogenes are frequently targeted by mutations that affect the sequence of their degrons or their cognate E3 ubiquitin ligases, causing an abnormal increase in their protein abundance. Overall, an important number of driver mutations across primary tumors affect either degrons or E3-ubiquitin ligases.
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