Inducing mortality by targeting mortalin

Abstract

Cancer Oncogenic mutations in the kinase BRAF can enhance cell survival, even in cells exposed to targeted inhibitors. Wu et al. found that a heat shock protein family A (HSP70)–related chaperone protein called mortalin disrupted a protein-protein interaction that would ordinarily trigger cell death in BRAF mutant cells. Depleting mortalin or treating cells with either HSP70 derivatives or synthetic decoy peptides that mimic mortalin target sites increased the efficacy of the BRAF inhibitor vemurafenib in cells and in tumor-bearing mice. Sci. Signal. 13 , eaay1478 (2020).