journal contribution
posted on 2023-04-04, 00:20 authored by Keelan Z. Guiley, Kevan M. Shokat Supplementary Figure S6: Western blots and for 28°C IP and CETSA (A) H1299 cells stably expressing p53 Y220C or p53 R273C were transferred from 37°C to 28°C and p21/MDM2 levels were monitored by western blot at the indicated time points. (B) U2OS cells stably expressing p53 Y220C or parent were transferred to a 28°C incubator and p21/MDM2 levels were observed by western blot at the indicated time points. (C) Extracts from H1299 cells expressing p53 Y220C incubated at 37°C or 28°C for 24 hr were immunoprecipitated with the WT conformation antibody Pab1620. (D) CETSA western blot for p53 Y220C DMSO. (E) CETSA western blot for p53 Y220C treated with 100 μM KG13 for 1 hr. (F) CETSA western blot for p53 WT DMSO.
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
