journal contribution
posted on 2023-04-04, 00:20 authored by Keelan Z. Guiley, Kevan M. Shokat Supplementary Figure S5: CDKN1A EMSA gels and intensity plots (A) EMSA for p53 WT-CL. (B) EMSA for p53 Y220C-CL. (C) EMSA for p53 Y220C-CL complexed with KG13. (D) EMSA for p53 R273C-CL. (E) Upper band intensities plotted for each protein construct. (F) Upper band intensities plotted for p53 R273C-CL.
Funding
Howard Hughes Medical Institute (HHMI)
Samuel Waxman Cancer Research Foundation (SWCRF)
Emerald Foundation, Inc.
Damon Runyon Cancer Research Foundation (DRCRF)
History
ARTICLE ABSTRACT
The transcription factor and tumor suppressor protein p53 is the most frequently mutated and inactivated gene in cancer. Mutations in p53 result in deregulated cell proliferation and genomic instability, both hallmarks of cancer. There are currently no therapies available that directly target mutant p53 to rescue wild-type function. In this study, we identify covalent compsounds that selectively react with the p53 somatic mutant cysteine Y220C and restore wild-type thermal stability.
The tumor suppressor p53 is the most mutated gene in cancer, and yet no therapeutics to date directly target the mutated protein to rescue wild-type function. In this study, we identify the first allele-specific compound that selectively reacts with the cysteine p53 Y220C to rescue wild-type thermal stability and gene activation.See related commentary by Lane and Verma, p. 14.This article is highlighted in the In This Issue feature, p. 1
