The unfolded protein response supports cellular robustness as a broad-spectrum compensatory pathway.

Stress pathways monitor intracellular systems and deploy a range of regulatory mechanisms in response to stress. One of the best-characterized pathways, the unfolded protein response (UPR), is responsible for maintaining endoplasmic reticulum (ER) homeostasis. The highly conserved Ire1 branch regulates hundreds of gene targets by activating a UPR specific transcription factor. To understand how the UPR manages ER stress, a novel genetic approach was applied to reveal how the system corrects disequilibria. The data show that UPR can address a wide range of dysfunctions that is otherwise lethal if not for its intervention. Transcriptional profiling of stress alleviated cells shows that the program can be modulated, not just in signal amplitude, but also through differential target gene expression depending on the stress. The breadth of the functions mitigated by the UPR further supports its role as a major mechanism maintaining systems robustness. Genes expression from early log phase of ALG5, LHS1, and SCJ1 knockout cell and untreated and DTT-treated WT cells. RNA was prepared from independent triplicate samples.