ArticleProceedings of the National Academy of Sciences of the United States of America2003
Proteasome inhibitors disrupt the unfolded protein response in myeloma cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 287 papers, 1 of them a synthesis that pooled it.
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Who cites it
287 citing papers in PubMed, 1 synthesis or guideline pooled it, 597 citations in OpenAlex.
- Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization.International journal of molecular sciences · 2023Pooled it
- RBM39 modulates UPR signaling through alternative splicing of IRE1α/Genes & development · 2026Article
- IP3R2-mediated inter-organelle calcium signaling suppresses melanosome degradation.PLoS biology · 2026Article
- ULK4 and CDKN2A polymorphisms influence the risk of developing monoclonal gammopathy of undetermined significance.International journal of cancer · 2026Article
- Cyclin-Dependent Kinase 5 Contributes to Bruton's Tyrosine Kinase Inhibitor Resistance via the IRE1α/XBP1 Axis in Mantle Cell Lymphoma.Research square · 2026Article
- Article
- The Model Related to Hypoxia and Endoplasmic Reticulum Stress Predicting Prognosis and Immunotherapy Response in Uterine Corpus Endometrial Cancer.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Regulation of stress tolerance by CREB1 sustains multiple myeloma cell survival.Cell death & disease · 2026Article
- The immunoproteasome regulates ILC2 responses by modulating mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- A Novel Chemotherapy Combination to Enhance Proteotoxic Cell Death in Hepatocellular Carcinoma Experimental Models Without Killing Non-Cancer Cells.International journal of molecular sciences · 2025Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Endoplasmic reticulum stress disrupts signaling via altered processing of transmembrane receptors.Cell communication and signaling : CCS · 2025Article
- Targeting MTHFD2 alters metabolic homeostasis and synergizes with bortezomib to inhibit multiple myeloma.Cell death discovery · 2025Article
- IRE1α-XBP1 safeguards hematopoietic stem and progenitor cells by restricting pro-leukemogenic gene programs.Nature immunology · 2025Article
- Prognostic implications of MUC1 and XBP1 concordant expression in multiple myeloma: A retrospective study.PloS one · 2025Article
- Tubulin-Binding Region Modulates Cholesterol-Triggered Aggregation of Tau Proteins.Journal of neurochemistry · 2025Article
- Distinct pathway activities are associated with prognosis and response to bortezomib-containing treatment in MCL1-M based molecular subtypes of multiple myeloma.Annals of hematology · 2024Article
- Elucidation of molecular mechanisms by which amyloid βBiochimica et biophysica acta. Molecular and cell biology of lipids · 2024Article
- Descriptive Analysis of Adverse Events Reported for New Multiple Myeloma Medications Using FDA Adverse Event Reporting System (FAERS) Databases from 2015 to 2022.Pharmaceuticals (Basel, Switzerland) · 2024Article
227 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Novel agents that target the proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, have demonstrated remarkable therapeutic efficacy in multiple myeloma, a plasma cell malignancy. However, the mechanism by which these compounds act remains unknown. A signaling pathway called the unfolded protein response (UPR) allows cells to handle the proper folding of proteins. The transcription factor XBP-1, a regulator of the UPR, is also required for plasma cell differentiation, suggesting a link between the UPR and plasma cell differentiation. Here we show that proteasome inhibitors target XBP-1 and the UPR in myeloma cells. Proteasome inhibitors suppress the activity of the translumenal endoplasmic reticulum endoribonuclease/kinase, IRE1 alpha, to impair the generation of the active, spliced XBP-1 species and simultaneously stabilize the unspliced species that acts as a dominant negative. Myeloma cells rendered functionally deficient in XBP-1 undergo increased apoptosis in response to endoplasmic reticulum stress. Identification of compounds that target the activity of IRE1 alpha/XBP-1 may yield novel therapies for the treatment of multiple myeloma and other malignancies that rely on an intact UPR.
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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.