Wild-type p53 oligomerizes more efficiently than p53 hot-spot mutants and overcomes mutant p53 gain-of-function via a "dominant-positive" mechanism.

ABSTRACT: Human p53 protein acts as a transcription factor predominantly in a tetrameric form. Single residue changes, caused by hot-spot mutations of the TP53 gene in human cancer, transform wild-type (wt) p53 tumor suppressor proteins into potent oncoproteins - with gain-of-function, tumor-promoting activity. Oligomerization of p53 allows for a direct interplay between wt and mutant p53 proteins if both are present in the same cells - where a mutant p53's dominant-negative effect known to inactivate wt p53, co-exists with an opposite mechanism - a "dominant-positive" suppression of the mutant p53's gain-of-function activity by wt p53. In this study we determine the oligomerization efficiency of wt and mutant p53 in living cells using FRET-based assays and describe wt p53 to be more efficien

SUBMITTER: Walerych D 

PROVIDER: S-EPMC6112834 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature