[HTML][HTML] Protein kinase R-like ER kinase and its role in endoplasmic reticulum stress-decided cell fate

Z Liu, Y Lv, N Zhao, G Guan, J Wang - Cell death & disease, 2015 - nature.com
Z Liu, Y Lv, N Zhao, G Guan, J Wang
Cell death & disease, 2015nature.com
Over the past few decades, understandings and evidences concerning the role of
endoplasmic reticulum (ER) stress in deciding the cell fate have been constantly growing.
Generally, during ER stress, the signal transductions are mainly conducted by three ER
stress transducers: protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-
requiring kinase 1 (IRE1) and activating transcription factor 6 (ATF6). Consequently, the
harmful stimuli from the ER stress transducers induce apoptosis and autophagy, which …
Abstract
Over the past few decades, understandings and evidences concerning the role of endoplasmic reticulum (ER) stress in deciding the cell fate have been constantly growing. Generally, during ER stress, the signal transductions are mainly conducted by three ER stress transducers: protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring kinase 1 (IRE1) and activating transcription factor 6 (ATF6). Consequently, the harmful stimuli from the ER stress transducers induce apoptosis and autophagy, which share several crosstalks and eventually decide the cell fate. The dominance of apoptosis or autophagy induced by ER stress depends on the type and degree of the stimuli. When ER stress is too severe and prolonged, apoptosis is induced to eliminate the damaged cells; however, when stimuli are mild, cell survival is promoted to maintain normal physiological functions by inducing autophagy. Although all the three pathways participate in ER stress-induced apoptosis and autophagy, PERK shows several unique characteristics by interacting with some specific downstream effectors. Notably, there are some preliminary findings on PERK-dependent mechanisms switching autophagy and apoptosis. In this review, we particularly focused on the novel, intriguing and complicated role of PERK in ER stress-decided cell fate, and also discussed more roles of PERK in restoring cellular homeostasis. However, more in-depth knowledge of PERK in the future would facilitate our understanding about many human diseases and benefit in searching for new molecular therapeutic targets.
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