Protein folding, assembly and transport. Other pathological stimuli interrupt the process of protein folding and then End to accumulation of unfolded or misfolded proteins In the ER, a condition known as ER stress. These pathological stimuli are those that depletion of ER calcium ver Changed glycosylation, N hrstoffmangel Cause oxidative stress, DNA Sch The, or interruption of the power or fluctuations. Manage the accumulation of unfolded or misfolded proteins, a group of functions ER signaling, which is collectively known as the unfolded protein response, Modifies the programs of transcription and translation to ER Hom Maintain homeostasis. GSK1070916 UPR has two main functions: first, in order to restore the normal function of the cell by stopping protein translation and activation of the signaling pathways that lead to an increased FITTINGS production of molecular chaperones in protein folding involved are two initiate to apoptotic pathways to the stressed cells w During the first targets not achieved continued removal within a specified period or interruption. As part of the UPR, the ER-associated protein degradation is responsible for the degradation of misfolded or aberrant proteins ER, makes an important mechanism of protein folding with quality Embroidered t. W Recogn during the process of ERAD, molecular chaperones and associated factors And its target substrates for retrotranslocation to the cytoplasm where they are polyubiquitinated and degraded by the 26S proteasome.
ERAD is essential for maintaining the Hom ER homeostasis, and disruption of ERAD is closely associated with apoptosis induced by ER stress related. Degradation by the proteasome and autophagy were identified as the two mechanisms responsible for the release of the protein in stressed cells. Ubiquitin-proteasome degradation of l Soluble proteins combined condensed. Autophagy involves cytoplasmic components engulfed in a double membrane vesicles. Maturation of these vesicles Pazopanib with lysosomes, which merge in a deterioration of the components autophagosome degradation by lysosomal enzymes. Conditions that induce ER stress also lead to induction of autophagy. The activation of IRE1, eIF2a phosphorylation and ER Ca2 release can k Regulate all autophagy. The activation of autophagy by ER stress can be either protective or cytotoxic cell. Persistent ER stress on the cytoprotective functions of UPR and autophagy in cell death programs. Some antitumor agents activate ER stress and autophagy as an important mechanism for cancer cell death f rdern. 1.1. The unfolded protein response pathways relating to the aggregation of unfolded proteins, GRP78, one of the h Most common occurring ER luminal chaperones, binds to unfolded proteins And distances itself from the membrane three ER stress sensors connected. That Ren Dehnungsme go Streak pancreatic ER ER kinase kinase, the activation of transcription factor 6, and inositol requiring enzyme. The dissociation of GRP78 from these stress sensors erm glicht Their subsequent Border activation. It has been suggested that the activation of ER stress sensors occur sequentially, with PERK the first, quickly followed by ATF6 and IRE1 are activated last. Activated PERK Bl Press protein synthesis by phosphorylation general