Abstract
The unfolded protein response (UPR) is an evolutionarily conserved adaptive regulatory pathway that alleviates protein-folding defects in the endoplasmic reticulum (ER). Physiological demands, environmental perturbations and pathological conditions can cause accumulation of unfolded proteins in the ER and the stress signal is transmitted to the nucleus to turn on a series of genes to respond the challenge. In metazoan, the UPR pathways consisted of IRE1/XBP1, PEK-1 and ATF6, which function in parallel and downstream transcriptional activation triggers the proteostasis networks consisting of molecular chaperones, protein degradation machinery and other stress response pathways ((Labbadia J, Morimoto RI, F1000Prime Rep 6:7, 2014); (Shen X, Ellis RE, Lee K, Annu Rev Biochem 28:893-903, 2014)). The integrated responses act on to resolve the ER stress by increasing protein folding capacity, attenuating ER-loading translation, activating ER-associated proteasomal degradation (ERAD), and regulating IRE1-dependent decay of mRNA (RIDD). Therefore, the effective UPR to internal and external causes is linked to the multiple pathophysiological conditions such as aging, immunity, and neurodegenerative diseases. Recent development in the research of the UPR includes cell-nonautonomous features of the UPR, interplay between the UPR and other stress response pathways, unconventional UPR inducers, and noncanonical UPR independent of the three major branches, originated from multiple cellular and molecular machineries in addition to ER. Caenorhabditis elegans model system has critically contributed to these unprecedented aspects of the ER UPR and broadens the possible therapeutic targets to treat the ER-stress associated human disorders and time-dependent physiological deterioration of aging.
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Abbreviations
- 4E-BP:
-
4E-binding protein
- AIRAP:
-
arsenic-inducible proteasomal 19S regulatory particle-associated protein
- COPII:
-
coatomer protein complex II
- DIC:
-
differential interference contrast
- DR:
-
dietary restriction
- ECM:
-
extracellular matrix
- ERAD:
-
ER-associated proteasomal degradation
- ERES:
-
ER-exit sites
- ETA:
-
ethanolamine
- gf:
-
gain-of-function
- GlcNAc:
-
N-acetylglucosamine
- HA:
-
hyaluronan
- HAase:
-
hyaluronidase
- HIF-1:
-
hypoxia-inducible factor-1
- HP1:
-
heterochromatin protein 1
- HPL-2:
-
heterochromatin protein like-2
- KO:
-
knockout
- LBS:
-
lipid bilayer stress
- lf:
-
loss-of-function
- MAPK:
-
mitogen-activated protein kinase
- NAC:
-
nascent polypeptide-associated complex
- NMD:
-
nonsense-mediated mRNA decay
- NMHCIIB:
-
nonmuscle myosin heavy chain IIB
- OQC:
-
oxidative quality control
- PC:
-
phosphatidylcholine
- PD:
-
Parkinson disease
- PDI6:
-
disulfide isomerase 6
- PE:
-
phosphatidylethanolamine
- RIDD:
-
IRE-1-dependent decay of mRNA
- RNC:
-
ribosome-nascent chain complexes
- ROS:
-
reactive oxygen species
- S6K:
-
S6 kinase
- sams:
-
S-adenosyl methionine synthetase
- SCD:
-
stearoyl-CoA-desaturases
- SCV:
-
small clear vesicle
- SRP:
-
signal recognition particle
- SUMO:
-
small ubiquitin-like modifier
- TMEM2:
-
Transmembrane Protein 2
- TOR:
-
target of rapamycin
- UPR:
-
unfolded protein response
- VIT:
-
vitellogenin
- α-syn:
-
α-synuclein
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This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2018R1A2A3074987). I sincerely apologize our eminent colleagues in case unwittingly omitting their valuable works.
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Lee, SK. (2021). Endoplasmic Reticulum Homeostasis and Stress Responses in Caenorhabditis elegans. In: Agellon, L.B., Michalak, M. (eds) Cellular Biology of the Endoplasmic Reticulum . Progress in Molecular and Subcellular Biology, vol 59. Springer, Cham. https://doi.org/10.1007/978-3-030-67696-4_13
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