Figure 2

Schematic representation of secretion stress responses in eukaryotes Secretory proteins are translocated to the ER either during their translation or post-translationally. Folding of these proteins in the ER can be disturbed by environmental factors or it can be inhibited experimentally by agents inhibiting protein folding like dithiothreitol (DTT) and Ca-ionophores or agents inhibiting glycosylation like tunicamycin. It has been observed that foreign proteins often do not fold well and cause conformational stress. Several responses of the cell to impaired protein folding in the ER have been discovered: 1.) Unfolded protein response (UPR). Genes encoding folding helpers like the chaperone Bip and the foldase protein disulfide isomerase Pdi, and a large number of other genes involved in other functions of the secretory pathway are induced. The proteins Ire1 and Hac1 involved in this signal transduction pathway are shown in the figure. 2.) Translation attenuation. The translation initiation factor eIF2 alpha is phosphorylated, and subsequently translation initiation is inhibited. This reduces the influx of proteins into the ER. This response is only known from mammalian cells. 3.) Repression under secretion stress (RESS). The mRNA levels of genes encoding secreted proteins are down-regulated during ER stress. This response has been discovered in filamentous fungi, but there is evidence for its occurrence in plants.