ArticleProceedings of the National Academy of Sciences of the United States of America2008
Rationalizing translation attenuation in the network architecture of the unfolded protein response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
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- Mechanism of Decision Making between Autophagy and Apoptosis Induction upon Endoplasmic Reticulum Stress.International journal of molecular sciences · 2024Review
- A systems biological analysis of the ATF4-GADD34-CHOP regulatory triangle upon endoplasmic reticulum stress.FEBS open bio · 2022Article
- Temporal control of the integrated stress response by a stochastic molecular switch.Science advances · 2022Article
- ATF6 Is a Critical Determinant of CHOP Dynamics during the Unfolded Protein Response.iScience · 2020Article
- Induction of autophagy-dependent apoptosis in cancer cells through activation of ER stress: an uncovered anti-cancer mechanism by anti-alcoholism drug disulfiram.American journal of cancer research · 2019Article
- How to design an optimal sensor network for the unfolded protein response.Molecular biology of the cell · 2018Article
- A data-entrained computational model for testing the regulatory logic of the vertebrate unfolded protein response.Molecular biology of the cell · 2018Article
- Cell Signaling and Stress Responses.Cold Spring Harbor perspectives in biology · 2016Review
- Physiological modulation of BiP activity by trans-protomer engagement of the interdomain linker.eLife · 2015Article
- Chronic SIV and morphine treatment increases heat shock protein 5 expression at the synapse.Journal of neurovirology · 2015Article
- The role of endoplasmic reticulum stress in human pathology.Annual review of pathology · 2015Review
- Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1.Cell stem cell · 2014Article
- The ER stress response and host temperature adaptation in the human fungal pathogen Cryptococcus neoformans.Virulence · 2014Review
- The unfolded protein response in the protozoan parasite Toxoplasma gondii features translational and transcriptional control.Eukaryotic cell · 2013Article
- A mathematical model of the unfolded protein stress response reveals the decision mechanism for recovery, adaptation and apoptosis.BMC systems biology · 2013Article
- Endoplasmic reticulum stress-mediated hippocampal neuron apoptosis involved in diabetic cognitive impairment.BioMed research international · 2013Article
- Protein-folding homeostasis in the endoplasmic reticulum and nutritional regulation.Cold Spring Harbor perspectives in biology · 2012Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased levels of unfolded proteins in the endoplasmic reticulum (ER) of all eukaryotes trigger the unfolded protein response (UPR). Lower eukaryotes solely use an ancient UPR mechanism, whereby they up-regulate ER-resident chaperones and other enzymatic activities to augment protein folding and enhance degradation of misfolded proteins. Metazoans have evolved an additional mechanism through which they attenuate translation of secretory pathway proteins by activating the ER protein kinase PERK. In mammalian professional secretory cells such as insulin-producing pancreatic beta-cells, PERK is highly abundant and crucial for proper functioning of the secretory pathway. Through a modeling approach, we propose explanations for why a translation attenuation (TA) mechanism may be critical for beta-cells, but is less important in nonsecretory cells and unnecessary in lower eukaryotes such as yeast. We compared the performance of a model UPR, both with and without a TA mechanism, by monitoring 2 variables: (i) the maximal increase in ER unfolded proteins during a response, and (ii) the accumulation of chaperones between 2 consecutive pulses of stress. We found that a TA mechanism is important for minimizing these 2 variables when the ER is repeatedly subjected to transient unfolded protein stresses and when it sustains a large flux of secretory pathway proteins which are both conditions encountered physiologically by pancreatic beta-cells. Low expression of PERK in nonsecretory cells, and its absence in yeast, can be rationalized by lower trafficking of secretory proteins through their ERs.
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