期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 24, 页码 -出版社
MDPI
DOI: 10.3390/ijms20246197
关键词
mutant p53; gain of function; tumorigenesis; p53 reactivation; p53 network
资金
- Israel Science Foundation (ISF)
- Flight Attendant Medical Research Institute (FAMRI)
The p53 protein is mutated in about 50% of human cancers. Aside from losing the tumor-suppressive functions of the wild-type form, mutant p53 proteins often acquire inherent, novel oncogenic functions, a phenomenon termed mutant p53 gain-of-function (GOF). A growing body of evidence suggests that these pro-oncogenic functions of mutant p53 proteins are mediated by affecting the transcription of various genes, as well as by protein-protein interactions with transcription factors and other effectors. In the current review, we discuss the various GOF effects of mutant p53, and how it may serve as a central node in a network of genes and proteins, which, altogether, promote the tumorigenic process. Finally, we discuss mechanisms by which Mother Nature tries to abrogate the pro-oncogenic functions of mutant p53. Thus, we suggest that targeting mutant p53, via its reactivation to the wild-type form, may serve as a promising therapeutic strategy for many cancers that harbor mutant p53. Not only will this strategy abrogate mutant p53 GOF, but it will also restore WT p53 tumor-suppressive functions.
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