ArticlePloS one2010
Interplay of substrate retention and export signals in endoplasmic reticulum quality control.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- The generation of detergent-insoluble clipped fragments from an ERAD substrate in mammalian cells.Scientific reports · 2023Article
- Substrate ubiquitination retains misfolded membrane proteins in the endoplasmic reticulum for degradation.Cell reports · 2021Article
- Aneuploidy-induced proteotoxic stress can be effectively tolerated without dosage compensation, genetic mutations, or stress responses.BMC biology · 2020Article
- The degradation-promoting roles of deubiquitinases Ubp6 and Ubp3 in cytosolic and ER protein quality control.PloS one · 2020Article
- Protein quality control in the secretory pathway.The Journal of cell biology · 2019Review
- Article
- The glycan-dependent ERAD machinery degrades topologically diverse misfolded proteins.The Plant journal : for cell and molecular biology · 2018Article
- Protein sorting at the ER-Golgi interface.The Journal of cell biology · 2016Review
- Analysis of COPII Vesicles Indicates a Role for the Emp47-Ssp120 Complex in Transport of Cell Surface Glycoproteins.Traffic (Copenhagen, Denmark) · 2016Article
- Protein folding and secretion: mechanistic insights advancing recombinant protein production in S. cerevisiae.Current opinion in biotechnology · 2014Review
- Luminal Ca2+ depletion during the unfolded protein response in Xenopus oocytes: cause and consequence.Cell calcium · 2013Article
- The endoplasmic reticulum-associated degradation pathways of budding yeast.Cold Spring Harbor perspectives in biology · 2012Review
- Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation.Molecular biology of the cell · 2012Article
- Endoplasmic reticulum stress regulation of the Kar2p/BiP chaperone alleviates proteotoxicity via dual degradation pathways.Molecular biology of the cell · 2012Article
- Endoplasmic reticulum-associated degradation of glycoproteins in plants.Frontiers in plant science · 2012Article
- Endoplasmic reticulum-associated degradation (ERAD) and free oligosaccharide generation in Saccharomyces cerevisiae.The Journal of biological chemistry · 2011Article
- Protein folding and quality control in the endoplasmic reticulum: Recent lessons from yeast and mammalian cell systems.Current opinion in cell biology · 2011Review
- Enhancing Yeast Surface Display: UPR, ERAD, and ER Dynamics in Recombinant Protein Production.Food technology and biotechnologyReview
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
backgroundEndoplasmic reticulum (ER) quality control mechanisms are part of a comprehensive system to manage cell stress. The flux of molecules is monitored to retain folding intermediates and target misfolded molecules to ER-associated degradation (ERAD) pathways. The mechanisms of sorting remain unclear. While some proteins are retained statically, the classical model substrate CPY* is found in COPII transport vesicles, suggesting a retrieval mechanism for retention. However, its management can be even more dynamic. If ERAD is saturated under stress, excess CPY* traffics to the vacuole for degradation. These observations suggest that misfolded proteins might display different signals for their management. METHODOLOGY/PRINCIPAL
findingsHere, we report the existence of a functional ER exit signal in the pro-domain of CPY*. Compromising its integrity causes ER retention through exclusion from COPII vesicles. The signal co-exists with other signals used for retention and degradation. Physiologically, the export signal is important for stress tolerance. Disabling it converts a benign protein into one that is intrinsically cytotoxic. CONCLUSIONS/SIGNIFICANCE: These data reveal the remarkable interplay between opposing signals embedded within ERAD substrate molecules and the mechanisms that decipher them. Our findings demonstrate the diversity of mechanisms deployed for protein quality control and maintenance of protein homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.