| First Author | Lu M | Year | 2014 |
| Journal | Science | Volume | 345 |
| Issue | 6192 | Pages | 98-101 |
| PubMed ID | 24994655 | Mgi Jnum | J:212074 |
| Mgi Id | MGI:5578049 | Doi | 10.1126/science.1254312 |
| Citation | Lu M, et al. (2014) Cell death. Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis. Science 345(6192):98-101 |
| abstractText | Protein folding by the endoplasmic reticulum (ER) is physiologically critical; its disruption causes ER stress and augments disease. ER stress activates the unfolded protein response (UPR) to restore homeostasis. If stress persists, the UPR induces apoptotic cell death, but the mechanisms remain elusive. Here, we report that unmitigated ER stress promoted apoptosis through cell-autonomous, UPR-controlled activation of death receptor 5 (DR5). ER stressors induced DR5 transcription via the UPR mediator CHOP; however, the UPR sensor IRE1alpha transiently catalyzed DR5 mRNA decay, which allowed time for adaptation. Persistent ER stress built up intracellular DR5 protein, driving ligand-independent DR5 activation and apoptosis engagement via caspase-8. Thus, DR5 integrates opposing UPR signals to couple ER stress and apoptotic cell fate. |
