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].