Proteomic identification of ERP29 as a key chemoresistant factor activated by the aggregating p53 mutant Arg282Trp.

摘要: Mutation of the TP53 gene represents a prevalent genetic alteration in human cancers, and subset p53 mutants may form amyloid-like aggregates that contribute to gain oncogenic functions (GOFs) chemoresistance. Here we identify pathways mediate aggregation-associated GOF by using combined proteomic analysis genome-wide recruitment profiling. Mass spectrometry revealed activation unfolded protein response (UPR) pathway upregulation endoplasmic reticulum 29 (ERp29) R282WTP53-expressing cells were exposed cisplatin stress. Chromatin immunoprecipitation sequencing identified significant 'CCCASS' binding motif Arg282Trp, which is present promoter region ERP29 gene. The mutant upregulated mRNA expression levels, whereas targeting specific small interfering RNAs suppressed chemoresistant effect Arg282Trp. anti-aggregation peptide ReACp53 significantly decreased effect. These findings highlight role acquired chemoresistance cancer expressing aggregating Our results also suggest ERP29-mediated can be targeted ReACp53.