A mathematical model of the unfolded protein stress response reveals the decision mechanism for recovery adaptation and apoptosis

摘要

BackgroundThe unfolded protein response (UPR) is a major signalling cascade acting in the quality control of protein folding in the endoplasmic reticulum (ER). The cascade is known to play an accessory role in a range of genetic and environmental disorders including neurodegenerative and cardiovascular diseases, diabetes and kidney diseases. The three major receptors of the ER stress involved with the UPR, i.e. IRE1 α, PERK and ATF6, signal through a complex web of pathways to convey an appropriate response. The emerging behaviour ranges from adaptive to maladaptive depending on the severity of unfolded protein accumulation in the ER; however, the decision mechanism for the switch and its timing have so far been poorly understood.