Cancer-derived C-terminus-extended p53 mutation confers dominant-negative effect on its wild-type counterpart  

作　　者：Shibo Huang Bo Cao Jieqiong Wang Yiwei Zhang Elisa Ledet Oliver Sartor Yuqin Xiong Shelya X.Zeng Hua Lu 

机构地区：[1]Institute of Clinical Pharmacology,Nanchang University,Nanchang 330006,China [2]Department of Biochemistry&Molecular Biology,Tulane University School of Medicine,New Orleans,LA 70112,USA [3]Tulane Cancer Center,Tulane University School of Medicine,New Orleans,LA 70112,USA [4]College of Pharmacy,Xavier University of Louisiana,New Orleans,LA 70125,USA

出　　处：《Journal of Molecular Cell Biology》2022年第1期11-20,共10页分子细胞生物学报（英文版）

摘　　要：The vast majority of p53 missense mutants lose the wild-type (wt) function and/or exert ‘dominant-negative’ effects on their wt counterpart. Here, we identify a novel form of p53 mutation with an extended C-terminus (p53 long C-terminus, p53LC) in a variety of human cancers. Interestingly, the two representative mutants (named ‘p53-374*48’ and ‘p53-393*78’) as tested in this study show both loss-of-function and dominant-negative phenotypes in cell proliferation and colony formation assays. Mechanistically, p53LCs interact with and retain wt p53 in the cytoplasm and prevent it from binding to the promoters of target genes, consequently inhibiting its transcriptional activity. Also, p53LCs are very stable, though not acetylated in cells. Remarkably, the p53LCs can desensitize wt p53-containing cancer cells to p53-activating agents. Together, our results unveil a longer form of p53 mutant that possesses a dominant-negative effect on its wt counterpart, besides losing its wt activity.

关 键 词：mutant p53-393*78 mutant p53-374*48 P53 longer C-terminus p53 dominant-negative effect drug resistance ACETYLATION 

分 类 号：Q2[生物学—细胞生物学]