Investigation of the Molecular Mechanisms Leading to Protein Translation Inhibition in Response to Endoplasmic Reticulum Stress
DOI:
https://doi.org/10.54172/mjsc.v33i3.192Keywords:
ER stress, PERK, Translation, UPR, Protein synthesis, Firefly, Renilla, MIN6Abstract
Protein folding is an important process for cellular function. ER is responsible for the synthesis, folding, modification, and quality control of numerous secretory and membrane proteins. The intracellular disturbance caused by different stressors leading to the accumulation of unfolded/ misfolded proteins can all lead to an alteration in ER homeostasis. If the unfolded/misfolded proteins continue to accumulate inside the ER, the unfolded protein response (UPR) is induced to overcome this situation. UPR acts by three different mechanisms:(1) increase the ER protein-folding capacity (Robertsonand Branch, 1987),(2) reduce global protein synthesis, and (3) enhance ER-associated degradation process. The UPR is mediated by three ER transmembrane protein sensors: (1) activating transcription factor 6 (ATF6), (2) inositol requiring kinase 1(IRE1), and (3) double-stranded RNA-activated protein kinase (PKR) like endoplasmic reticulum kinase (PERK). Each sensor of the UPR protein responds to the certain level of unfolded/misfolded protein in the ER. If the cell fails to restore or overcome the protein-folding defect, cell-death signaling pathways are activated.
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