ArticleProceedings of the National Academy of Sciences of the United States of America2017
Suppression of 19S proteasome subunits marks emergence of an altered cell state in diverse cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- The 19S proteasome as a therapeutic target in hematologic malignancies.Frontiers in cell and developmental biology · 2026Review
- Epigenetic regulation of cuproptosis in cancer: mechanisms, microenvironment, and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- More 26S and 30S proteasomes are beneficial in proteinopathy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ubiquitin proteasome system (UPS): a crucial determinant of the epigenetic landscape in cancer.Epigenomics · 2025Review
- Spatial mechanisms of quality control during chaperone-mediated assembly of the proteasome.Nature communications · 2025Article
- An up-To-Date Review of Elesclomol and Its Nano-Formulations in Cancer Therapy.Cancer reports (Hoboken, N.J.) · 2025Review
- Loss of correlated proteasomal subunit expression selectively promotes the 20SCommunications biology · 2025Article
- Multifaceted role of GCN2 in tumor adaptation and therapeutic targeting.Translational oncology · 2024Review
- Thiolutin has complex effects in vivo but is a direct inhibitor of RNA polymerase II in vitro.Nucleic acids research · 2024Article
- Review
- The proteasome regulator PSME4 modulates proteasome activity and antigen diversity to abrogate antitumor immunity in NSCLC.Nature cancer · 2023Article
- Article
- The molecular mechanism and challenge of targeting XPO1 in treatment of relapsed and refractory myeloma.Translational oncology · 2022Review
- Assembly checkpoint of the proteasome regulatory particle is activated by coordinated actions of proteasomal ATPase chaperones.Cell reports · 2022Article
- Metformin Induces Resistance of Cancer Cells to the Proteasome Inhibitor Bortezomib.Biomolecules · 2022Article
- Contribution of the Tumor Microenvironment to Metabolic Changes Triggering Resistance of Multiple Myeloma to Proteasome Inhibitors.Frontiers in oncology · 2022Review
- Article
- Identification of genes modulated by interferon gamma in breast cancer cells.Biochemistry and biophysics reports · 2021Article
- Targeting ubiquitin-specific protease-7 in plasmacytoid dendritic cells triggers anti-myeloma immunity.Leukemia · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of proteasome inhibitors to target cancer's dependence on altered protein homeostasis has been greatly limited by intrinsic and acquired resistance. Analyzing data from thousands of cancer lines and tumors, we find that those with suppressed expression of one or more 19S proteasome subunits show intrinsic proteasome inhibitor resistance. Moreover, such proteasome subunit suppression is associated with poor outcome in myeloma patients, where proteasome inhibitors are a mainstay of treatment. Beyond conferring resistance to proteasome inhibitors, proteasome subunit suppression also serves as a sentinel of a more global remodeling of the transcriptome. This remodeling produces a distinct gene signature and new vulnerabilities to the proapoptotic drug, ABT-263. This frequent, naturally arising imbalance in 19S regulatory complex composition is achieved through a variety of mechanisms, including DNA methylation, and marks the emergence of a heritably altered and therapeutically relevant state in diverse cancers.
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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.