It takes a team: a gairvof-function story of p53-R249S

作     者：Huai Wang Peng Liao Shelya X. Zeng Hua Lu 

作者机构：Department of Biochemistry and Molecular Biology Tulane Cancer Center Tulane University School of Medicine New Orleans LA 70112 USA School of Public Health Nanchang University Nanchang 330006 China Jiangxi Provincial Key Laboratory of Preventive Medicine Nanchang University Nanchang 330006 China 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2019年第11卷第4期

页      面：277-283页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：H.W. was supported in part by China Scholarship Council (CSC) H.L. and S.X.Z. are supported in part by 

主　　题：p53-R249S Liver cancer HCC CDK4/cyclin D1 PIN1 c-Myc FBW7a 

摘      要：Gain-of-function (GOF), the most malicious oncogenic activity of a cancer-promoting protein, is well illustrated to three hotspot p53 mutations at R248, R175, and R273 with distinct molecular mechanisms. Yet, less is known about another hotspot p53 mutant, R249S (p53-R249S). p53-R249S is the sole hotspot mutation in hepatocellular carcinoma (HCC) that is highly associated with chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1). Its GOF is suggested by the facts that this mutant is associated with earlier onset of HCC and poorer prognosis of cancer patients and that its overexpression drives HCC proliferation and tumorigenesis. By contrast, simply knocking in this mutant in normal mice did not show apparent GOF activity. Hence, the GOF activity for p53-R249S and its underlying mechanisms have been elusive until recent findings offered some new insights. This review will discuss these findings as well as their clinical significance and implications for the development of a strategy to target multiple molecules as a therapy for p53-R249S-harboring HCC.