What happens during unfolded protein response?
In this scenario, the UPR has three aims: initially to restore normal function of the cell by halting protein translation, degrading misfolded proteins, and activating the signalling pathways that lead to increasing the production of molecular chaperones involved in protein folding.
What is the function of unfolded protein?
The UPR transmits information about protein folding status to the nucleus and cytosol to adjust the protein folding capacity of the cell or, in the event of chronic damage, induce apoptotic cell death.
Can the unfolded protein response lead to apoptosis?
However, if the overload of unfolded or misfolded proteins in the ER is not resolved, the prolonged UPR will induce ER stress-associated programmed cell death, apoptosis, to protect the organism by removing the stressed cells.
What is the function of IRE1 in the cell?
IRE1 is an ER transmembrane sensor that activates UPR to maintain ER and cellular function. While mammalian IRE1 promotes cell survive, it can initiate apoptosis via decay of anti-apoptotic microRNAs.
How is IRE1 activated?
Ire1 is activated in response to accumulation of misfolded proteins within the endoplasmic reticulum as part of the unfolded protein response (UPR). It is a unique enzyme, possessing both kinase and RNase activity that is required for specific splicing of Xbp1 mRNA leading to UPR activation.
What type of protein is IRE1?
ER transmembrane protein
As an ER transmembrane protein, IRE1 monitors ER homeostasis through an ER luminal stress-sensing domain and triggers UPR through a cytoplasmic kinase domain and an RNase domain [15, 16].
What activates IRE1?
How is IRE1 regulated by BiP?
One model proposes that Ire1 activity is mainly regulated by the ER-resident chaperone BiP (Kar2 in yeast). In this model, BiP inhibits Ire1 activity by binding to it in the absence of stress. During stress, BiP is titrated away by unfolded proteins, leaving Ire1 free to oligomerize and activate.