Mutant p53-Nrf2 axis regulates the proteasome machinery in cancer

Kamil Lisek; Dawid Walerych; Giannino Del Sal

doi:10.1080/23723556.2016.1217967

Mutant p53-Nrf2 axis regulates the proteasome machinery in cancer

Mol Cell Oncol. 2016 Sep 2;4(1):e1217967. doi: 10.1080/23723556.2016.1217967. eCollection 2017.

Authors

Kamil Lisek¹, Dawid Walerych¹, Giannino Del Sal²

Affiliations

¹ Laboratorio Nazionale CIB, Area Science Park Padriciano , Trieste, Italy.
² Laboratorio Nazionale CIB, Area Science Park Padriciano, Trieste, Italy; Dipartimento di Scienze della Vita-Università degli Studi di Trieste, Trieste, Italy.

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 "bounce-back" response to proteasome inhibitors, can be overcome by targeting p53 mutant proteins with APR-246/PRIMA-1Met.

Keywords: APR-246; Chip-seq; Keap1; Nrf2; TNBC; cancer; multi-omics; mutant p53; proteasome; proteomics; transcriptomics.