DR5 Disulfide Bonding Functions as a Sensor and Effector of Protein Folding Stress.

ABSTRACT: New agents are needed that selectively kill cancer cells without harming normal tissues. The TRAIL ligand and its receptors, DR5 and DR4, exhibit cancer-selective toxicity. TRAIL analogs or agonistic antibodies targeting these receptors are available but have not yet received FDA approval for cancer therapy. Small molecules for activating DR5 or DR4 independently of protein ligands may activate TRAIL receptors as a monotherapy or potentiate the efficacy of TRAIL analogs and agonistic antibodies. Previously described disulfide bond-disrupting agents activate DR5 by altering its disulfide bonding through inhibition of protein disulfide isomerases ERp44, AGR2, and PDIA1. Work presented in this article extends these findings by showing that disruption of single DR5 disulfide bonds causes high-

SUBMITTER: Law ME 

PROVIDER: S-EPMC11989202 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature