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: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers-State University o
• 出 处: 分子细胞生物学报（英文版）
• 发表日期: 2020年9期
• 关键词: tumor suppressor p53 mutation gain-of-function tumorigenesis cancer therapy

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 pro-gression,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 advan-ces in the studies on mutp53 regulation and GOF as well as therapies targeting mutp53 in human cancers.