Gain-of-function mutant p53 in cancer progression and therapy  

作　　者：Cen Zhang Juan Liu Dandan Xu Tianliang Zhang Wenwei Hu Zhaohui Feng 

机构地区：[1]1Department of Radiation Oncology,Rutgers Cancer Institute of New Jersey,Rutgers-State University of New Jersey,New Brunswick,NJ 08903,USA

出　　处：《Journal of Molecular Cell Biology》2020年第9期674-687,共14页分子细胞生物学报（英文版）

基　　金：This work was supported in part by grants from the National Institutes of Health(NIH;R01CA227912 and R01CA214746)to Z.F.and grants from NIH(R01CA203965);Congressionally Directed Medical Research Programs(CDMRP;W81XWH-16-1-0358 and W81XWH1810238)to W.H.

摘　　要：p53 is a key tumor suppressor,and loss of p53 function is frequently a prerequisite for cancer development.The p53 gene is the most frequently mutated gene in human cancers;p53 mutations occur in>50%of all human cancers and in almost every type of human cancers.Most of p53 mutations in cancers are missense mutations,which produce the full-length mutant p53(mutp53)protein with only one amino acid difference from wild-type p53 protein.In addition to loss of the tumor-suppressive function of wild-type p53,many mutp53 proteins acquire new oncogenic activities independently of wild-type p53 to promote cancer progression,termed gain-of-function(GOF).Mutp53 protein often accumulates to very high levels in cancer cells,which is critical for its GOF.Given the high mutation frequency of the p53 gene and the GOF activities of mutp53 in cancer,therapies targeting mutp53 have attracted great interest.Further understanding the mechanisms underlying mutp53 protein accumulation and GOF will help develop effective therapies treating human cancers containing mutp53.In this review,we summarize the recent advances in the studies on mutp53 regulation and GOF as well as therapies targeting mutp53 in human cancers.

关 键 词：tumor suppressor p53 MUTATION GAIN-OF-FUNCTION TUMORIGENESIS cancer therapy 

分 类 号：R730.2[医药卫生—肿瘤]