The endoplasmic-reticulum (ER) transmembrane protein IRE1 mitigates ER stress through kinase-ribonuclease and scaffolding activities. However, a significant nonenzymatic IRE1 dependency has been shown in cancer. Here, the authors design a proteolysis-targeting chimera (PROTAC) to fully disrupt cellular IRE1 protein, selectively blocking growth of IRE1-dependent cancer cells.
- Jin Du
- Elisia Villemure
- Avi Ashkenazi