Endoplasmic reticulum stress proteins (ER stress proteins)

Endoplasmic reticulum (ER) stress proteins are a specialized group of signaling molecules and chaperones that orchestrate the Unfolded Protein Response (UPR) to maintain cellular proteostasis (Source: PubMed, PMID: 29440425). The three primary sensors located in the ER membrane are Protein kinase RNA-like endoplasmic reticulum kinase (PERK), Inositol-requiring enzyme 1 alpha (IRE1α), and Activating transcription factor 6 (ATF6). Under physiological conditions, these sensors are maintained in an inactive state by the chaperone Binding immunoglobulin protein (BiP/GRP78) (Source: UniProt, P11021). When misfolded proteins accumulate, BiP dissociates to assist in folding, thereby activating the sensors to initiate downstream signaling that reduces global protein synthesis and increases the expression of folding catalysts. If the stress is chronic or severe, the pathway shifts from a pro-survival adaptive response to a pro-apoptotic signal, primarily mediated by the induction of C/EBP homologous protein (CHOP) (Source: PubMed, PMID: 25455068). These proteins are critical therapeutic targets in oncology, where cancer cells utilize the UPR to survive harsh microenvironments, and in neurodegeneration, where protein aggregation causes chronic ER stress. Pharmacological agents such as chemical chaperones (e.g., 4-phenylbutyric acid) or specific kinase inhibitors (e.g., GSK2606414) are being investigated to modulate these pathways for therapeutic benefit (Source: PubChem).

Other names

Unfolded protein response proteinsUPR proteinsER stress-related proteinsER stress sensors

Modulation of the unfolded protein response (UPR) signaling pathways to restore endoplasmic reticulum proteostasis or trigger programmed cell death in terminally stressed cells.