ArticleEMBO reports2021
Reflux of Endoplasmic Reticulum proteins to the cytosol inactivates tumor suppressors.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed.
- HSP60 and HSP10 depletion provoke distinct biological responses.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Article
- p38β-mediated BiP phosphorylation drives stemness and chemoresistance by suppressing UPR activation in hepatocellular carcinoma.Nature communications · 2026Article
- Protein Disulfide Isomerase Disassembles TDP-43/G3BP1 Condensates and Antagonizes TDP-43 Pathological Aggregates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endoplasmic reticulum and Golgi stress signaling-mediated regulation of protein secretion.Cellular & molecular biology letters · 2026Review
- BIP orchestrates bidirectional ER protein trafficking via co-chaperone complexes.Cellular & molecular biology letters · 2026Article
- Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.Biochemistry · 2026Review
- Article
- Within and beyond the boundaries of proteasomal assembly: PSMD9 chaperone as a multifunctional protein.Essays in biochemistry · 2025Review
- Non-genetic inactivation of caspase-3 and P53 increases cancer cell fitness by PDIA4 redistribution.Oncogene · 2025Article
- Agr2 in cancer and beyond: unraveling its role during protein synthesis, ER stress, and as a predictive biomarker.Molecular and cellular biochemistry · 2025Review
- Spatial protein redistribution: wandering but not lost.Cellular and molecular life sciences : CMLS · 2025Review
- Stress-induced translocation of the endoplasmic reticulum chaperone GRP78/BiP and its impact on human disease and therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Macrophages release neuraminidase and cleaved calreticulin for programmed cell removal.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Less is better: various means to reduce protein load in the endoplasmic reticulum.The FEBS journal · 2025Review
- Characterization of the AGR2-NPM3 axis uncovers the AGR2 involvement in PD-L1 regulation in colorectal cancer.Scientific reports · 2024Article
- AGR2: The Covert Driver and New Dawn of Hepatobiliary and Pancreatic Cancer Treatment.Biomolecules · 2024Review
- ER chaperone GRP78/BiP translocates to the nucleus under stress and acts as a transcriptional regulator.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Anterior gradient proteins in gastrointestinal cancers: from cell biology to pathophysiology.Oncogene · 2022Review
- Disulfiram Oxy-Derivatives Suppress Protein Retrotranslocation across the ER Membrane to the Cytosol and Initiate Paraptosis-like Cell Death.Membranes · 2022Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
In the past decades, many studies reported the presence of endoplasmic reticulum (ER)-resident proteins in the cytosol. However, the mechanisms by which these proteins relocate and whether they exert cytosolic functions remain unknown. We find that a subset of ER luminal proteins accumulates in the cytosol of glioblastoma cells isolated from mouse and human tumors. In cultured cells, ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. Using the ER luminal protein anterior gradient 2 (AGR2) as a proof of concept, we tested whether the refluxed proteins gain new functions in the cytosol. We find that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53. These data suggest that ER reflux constitutes an ER surveillance mechanism to relieve the ER from its contents upon stress, providing a selective advantage to tumor cells through gain-of-cytosolic functions-a phenomenon we name ER to Cytosol Signaling (ERCYS).
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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.