The secretory capacity of a cell is constantly challenged by physiological demands and pathological perturbations. To adjust and match the protein-folding capacity of the endoplasmic reticulum (ER) to changing secretory needs, cells employ a dynamic intracellular signaling pathway known as the unfolded protein response (UPR). Homeostatic activation of the UPR enforces adaptive programs that modulate and augment key aspects of the entire secretory pathway, whereas maladaptive UPR outputs trigger apoptosis. Here, we discuss recent advances into how the UPR integrates information about the intensity and duration of ER stress stimuli in order to control cell fate. These findings are timely and significant because they inform an evolving mechanistic understanding of a wide variety of human diseases, including diabetes mellitus, neurodegeneration, and cancer, thus opening up the potential for new therapeutic modalities to treat these diverse diseases.

细胞的分泌能力不断受到生理需求和病理扰动的挑战。为了调节和匹配内质网（ER）的蛋白质折叠能力以适应不断变化的分泌需求，细胞采用了动态的细胞内信号传导途径，即未折叠的蛋白质反应（UPR）。UPR的稳态激活会执行适应性程序，该程序可调节和增强整个分泌途径的关键方面，而适应不良的UPR输出会触发细胞凋亡。在这里，我们讨论了UPR如何整合有关ER应激刺激的强度和持续时间的信息以控制细胞命运的最新进展。这些发现之所以及时而有意义，是因为它们为各种人类疾病（包括糖尿病，神经退行性疾病，