Unfolded Protein Response

Abstract

The unfolded protein response is a regulatory mechanism that enhances the expression of proteins involved in the function of the endoplasmic reticulum (ER), including ER chaperones as well as components of ER-associated degradation, when eukaryotic cells increase the production of secretory proteins and the capacity of the ER function is overwhelmed. Without proper functioning of the unfolded protein response, secretory recombinant proteins produced in the ER cannot be correctly folded, are detained in the ER, and evoke ER stress, resulting in apoptotic cell death. Thus, the unfolded protein response is one of the most critical elements for efficient production of recombinant proteins in eukaryotic cells. In this article, the basic information and recent progress in the unfolded protein response of yeast and mammals will be summarized. The mechanisms regulating the capacity of organelles other than the ER, such as the Golgi stress response, lysosome stress response, mitochondrial unfolded protein response, and peroxisomal stress response, will be described. This information will be beneficial to construct ‘suprasecretory cells’, which acquire enormous capacity to produce recombinant secretory proteins indispensable in the biotechnology industry.