Mutant p53–Nrf2 axis regulates the proteasome machinery in cancer

Abstract

The proteasome machinery is a common target of gain-of-function p53 missense mutants. Upregulation of the proteasome fosters chemoresistance to proteasome inhibitors. In triple negative breast cancer cells this resistance mechanism, namely the Nrf2-regulated "<i>bounce-back</i>" response to proteasome inhibitors, can be overcome by targeting p53 mutant proteins with APR-246/PRIMA-1Met.