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Updated: Aug 5, 2026
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Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
ER-localized translational control as a nexus for proteostasis
Hideki Nishitoh1, Hisae Kadowaki1
1Laboratory of Biochemistry and Molecular Biology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
The FEBS Journal
|July 28, 2026
Summary
Cellular protein quality control (QC) at the endoplasmic reticulum (ER) membrane integrates multiple pathways to maintain homeostasis. This review highlights how ER-localized QC networks prevent disease by coordinating translation and protein folding.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Proteostasis is crucial for cellular and organismal health, with its disruption linked to human diseases.
- The endoplasmic reticulum (ER) is a key organelle for protein synthesis, folding, and trafficking, acting as a central hub for proteostasis.
- The ER membrane integrates translational regulation, RNA surveillance, and protein quality control (QC) pathways.
Purpose of the Study:
- To review recent advances in ER-localized translational control.
- To discuss how integrated QC networks on the ER membrane maintain proteostasis.
- To explore the role of these networks in disease pathogenesis.
Main Methods:
- This review synthesizes findings from recent studies on ER-associated protein quality control.
- It examines pathways including the integrated stress response (ISR), regulated IRE1-dependent decay (RIDD), nonsense-mediated mRNA decay (NMD), ribosome-associated QC (RQC), and ER-phagy.
- Emphasis is placed on the role of ubiquitin-fold modifier 1 conjugation (UFMylation) in linking these pathways.
Main Results:
- ER-localized QC pathways cooperate on or near the ER membrane to regulate translation, mRNA degradation, and protein folding.
- These integrated networks prevent the accumulation of aberrant proteins during ER-associated translation.
- UFMylation emerges as a key mechanism connecting ER-associated RQC, translocation-associated QC (TAQC), and ER-phagy.
Conclusions:
- Integrated QC networks at the ER membrane are essential for maintaining cellular proteostasis.
- Dysfunction of these ER-localized translational QC pathways contributes to various diseases, including neurodegeneration, inflammation, cancer, and aging.
- Understanding these pathways offers insights into disease mechanisms and potential therapeutic targets.
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