The unfolded protein response (UPR) is an intracellular signaling pathway that regulates the cellular response to the accumulation of misfolded proteins in eukaryotes. Our group has demonstrated that cell wall stress activates UPR in yeast through signals transmitted by the cell wall integrity (CWI) mitogen-activated protein (MAP) kinase cascade. The UPR is required to maintain cell wall integrity; mutants lacking a functional UPR have defects in cell wall biosynthesis and are hypersensitive to cell wall-directed antifungal drugs. Since ER stress also activates CWI signaling, we propose that ER and cell wall stress responses are coordinated by CWI and UPR signaling pathways in order to protect cells against these related stressors. Further investigation of the mechanisms of this coordinate regulation may lead to improved cell wall-directed antifungal therapies.
Keywords: ER stress; unfolded protein response; yeast cell wall.