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Rapid In Vivo Fixation and Isolation of Translational Complexes from Eukaryotic Cells
Published on: December 25, 2021
Translational control and the unfolded protein response
Ronald C Wek1, Douglas R Cavener
1Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. rwek@iupui.edu
Antioxidants & Redox Signaling
|September 1, 2007
Summary
The unfolded protein response (UPR) uses PERK (protein kinase R-like endoplasmic reticulum kinase) to control protein synthesis during cellular stress. This pathway helps cells adapt to endoplasmic reticulum stress and impacts disease.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Cellular stresses can overwhelm the secretory pathway, triggering the unfolded protein response (UPR).
- The UPR is a critical cellular defense mechanism involving translational and transcriptional regulation.
- Protein misfolding in the endoplasmic reticulum (ER) is a key stress signal.
Purpose of the Study:
- To review the mechanisms of PERK (EIF2AK3) activation and function in the UPR.
- To highlight PERK's role in regulating global and gene-specific translation during ER stress.
- To discuss PERK's contribution to cellular adaptation and disease.
Main Methods:
- Review of existing literature on the unfolded protein response and PERK signaling.
- Analysis of molecular mechanisms underlying PERK activation by misfolded proteins.
- Examination of translational and transcriptional control by PERK.
Main Results:
- PERK activation, via eIF2 phosphorylation, reduces global protein synthesis and enhances ER capacity.
- PERK promotes the translation of specific stress-related mRNAs, such as ATF4.
- Reduced protein synthesis facilitates the activation of transcription factors like NF-κB.
Conclusions:
- PERK is a central regulator of the UPR, balancing protein synthesis and cellular adaptation.
- PERK's function is crucial for managing ER stress and preventing cellular injury.
- Dysregulation of PERK signaling is implicated in various disease states.
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