The stress sensors in UPR pathway
The UPR functions to maintain ER homeostasis in the presence of a high unfolded protein load. In this context, UPR reprograms and modulates several secretary pathway-related genes involved in protein entry to ER, folding, post-translational modifications, quality controlling, protein degradation, vascular trafficking, and lipid biogenesis[3]. There are some discrepancies between the numbers of sensor proteins that are involved in UPR in different eukaryotes. In higher eukaryotes, however, UPR is driven by three sensor proteins, namely; Inositol Requiring Enzyme 1 (IRE1), Protein Kinase RNA like ER kinase (PERK), and Activating Transcription Factor 6 (ATF6)[5]. They can sense abnormal conditions and regulate the expression of specific transcription factors and modulate downstream effectors/ signaling events associated with UPR, orchestrating the adaptations to ER stress[3], [5]. The IRE1 and PERK signaling cascade activate via oligomerization and autophosphorylation while ATP6 translocate to the Golgi apparatus and then activate through proteolytic cleavage[8].