ArticleNature structural & molecular biology2019
UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor.
Article in Nature structural & molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 240 papers.
What it found
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Who cites it
240 citing papers in PubMed, 394 citations in OpenAlex.
- Cell surface GRP78 and the UPR pathway as novel promising therapeutic targets in cancer: an insight into the treatment of acute leukemia by using GRP78-CART cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Translating the Crosstalk Between Unfolded Protein Response and Ferroptosis to Cancer Therapies.Current oncology reports · 2026Review
- Intracellular pathogen manipulation of ER-phagy: direct receptor targeting and indirect pathway perturbation.Medical microbiology and immunology · 2026Review
- Hydrophobic Tag Protein Degraders: An Emerging Therapeutic Strategy for Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- CReP-mediated control of eIF2α phosphorylation is a critical node in MYC-driven medulloblastoma.Nature communications · 2026Article
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- p38β-mediated BiP phosphorylation drives stemness and chemoresistance by suppressing UPR activation in hepatocellular carcinoma.Nature communications · 2026Article
- Immunoglobulin binding protein (BiP) forms two types of dimers.Protein science : a publication of the Protein Society · 2026Article
- Functional Proteomics and Biological Screening of Protein Misfolding Under ER Stress Conditions in a Neuroblastoma Cell Model.Current issues in molecular biology · 2026Article
- CRISPR-Based Gene Dependency Screens Reveal Mechanism of BRAF Inhibitor Resistance in Anaplastic Thyroid Cancer.Molecular carcinogenesis · 2026Article
- Disruption of thePathogens (Basel, Switzerland) · 2026Article
- Degradation of ACSL3 by influenza A virus shifts unfolded protein response from antiviral defense to viral evasion.Virologica Sinica · 2026Article
- Multifunctional nanotherapeutics for targeted modulation of endoplasmic reticulum stress to potentiate cancer therapy.Asian journal of pharmaceutical sciences · 2026Review
- Autophagy-Apoptosis Crosstalk in Cancer: Mechanisms, Signaling Pathways, and Therapeutic Targeting.Cancers · 2026Review
- Endoplasmic reticulum and Golgi stress signaling-mediated regulation of protein secretion.Cellular & molecular biology letters · 2026Review
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Unveiling Selenoprotein T as a novel regulator of cardiomyocyte senescence: pivotal role of the CD36 receptor in AC16 human cardiomyocytes.GeroScience · 2026Article
- Brucella Omp25 activates the unfolded protein response to promote intracellular proliferation and inflammation.The Journal of biological chemistry · 2026Article
- Tumor necrosis factor α-induced endoplasmic reticulum stress promotes airway smooth muscle cell proliferation.American journal of physiology. Lung cellular and molecular physiology · 2026Article
180 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
BiP is a major endoplasmic reticulum (ER) chaperone and is suggested to act as primary sensor in the activation of the unfolded protein response (UPR). How BiP operates as a molecular chaperone and as an ER stress sensor is unknown. Here, by reconstituting components of human UPR, ER stress and BiP chaperone systems, we discover that the interaction of BiP with the luminal domains of UPR proteins IRE1 and PERK switch BiP from its chaperone cycle into an ER stress sensor cycle by preventing the binding of its co-chaperones, with loss of ATPase stimulation. Furthermore, misfolded protein-dependent dissociation of BiP from IRE1 is primed by ATP but not ADP. Our data elucidate a previously unidentified mechanistic cycle of BiP function that explains its ability to act as an Hsp70 chaperone and ER stress sensor.
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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.