期刊
EMBO REPORTS
卷 17, 期 11, 页码 1542-1551出版社
WILEY
DOI: 10.15252/embr.201541956
关键词
160p53; GOFs; mutant p53; p53 isoforms; p53 mRNA
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) [15H0594]
- JSPS KAKENHI [15H05721]
- Fundacao para a Ciencia e a Tecnologia (FCT) [PTDC/BIM-ONC/4890/2014]
- Japan Society for the Promotion of Science (JSPS Postdoctoral Fellowship)
- AXA Research Fund
- Ichiro Kanehara Foundation
- Fundação para a Ciência e a Tecnologia [PTDC/BIM-ONC/4890/2014] Funding Source: FCT
- Grants-in-Aid for Scientific Research [15H05721, 15H05949] Funding Source: KAKEN
Wild-type p53 functions as a tumour suppressor while mutant p53 possesses oncogenic potential. Until now it remains unclear how a single mutation can transform p53 into a functionally distinct gene harbouring a new set of original cellular roles. Here we show that the most common p53 cancer mutants express a larger number and higher levels of shorter p53 protein isoforms that are translated from the mutated full-length p53 mRNA. Cells expressing mutant p53 exhibit gain-of-function cancer phenotypes, such as enhanced cell survival, proliferation, invasion and adhesion, altered mammary tissue architecture and invasive cell structures. Interestingly, 160p53-overexpressing cells behave in a similar manner. In contrast, an exogenous or endogenous mutant p53 that fails to express 160p53 due to specific mutations or antisense knock-down loses pro-oncogenic potential. Our data support a model in which gain-of-function phenotypes induced by p53 mutations depend on the shorter p53 isoforms. As a conserved wild-type isoform, 160p53 has evolved during millions of years. We thus provide a rational explanation for the origin of the tumour-promoting functions of p53 mutations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据