ArticleEBioMedicine2015
Bortezomib Amplifies Effect on Intracellular Proteasomes by Changing Proteasome Structure.
Article in EBioMedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
11 citing papers in PubMed, 18 citations in OpenAlex.
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- Mitochondrial degradation of metallothionein enables local zinc mobilization during zinc limitation.bioRxiv : the preprint server for biology · 2026Article
- SOD2 is a regulator of proteasomal degradation promoting an adaptive cellular starvation response.Cell reports · 2025Article
- Loss of correlated proteasomal subunit expression selectively promotes the 20SCommunications biology · 2025Article
- Bortezomib Inhibits Open Configurations of the 20S Proteasome.Journal of the American Society for Mass Spectrometry · 2024Article
- The Histone Deacetylase Inhibitor ITF2357 (Givinostat) Targets Oncogenic BRAF in Melanoma Cells and Promotes a Switch from Pro-Survival Autophagy to Apoptosis.Biomedicines · 2022Article
- Development of Resistance to Endoplasmic Reticulum Stress-Inducing Agents in Mouse Leukemic L1210 Cells.Molecules (Basel, Switzerland) · 2020Article
- Elucidating the beneficial effects of melphalan, adriamycin, and corticoids in combination with bortezomib against multiple myeloma in vitro.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- SNIPER(TACC3) induces cytoplasmic vacuolization and sensitizes cancer cells to Bortezomib.Cancer science · 2017Article
- Proteasome inhibition correlates with intracellular bortezomib concentrations but not with antiproliferative effects after bolus treatment in myeloma cell lines.Naunyn-Schmiedeberg's archives of pharmacology · 2016Article
- Proteasome inhibition by bortezomib: A left hook and a right punch.EBioMedicine · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The proteasome inhibitor Bortezomib is used to treat multiple myeloma (MM). Bortezomib inhibits protein degradation by inactivating proteasomes' active-sites. MM cells are exquisitely sensitive to Bortezomib - exhibiting a low-nanomolar IC(50) - suggesting that minimal inhibition of degradation suffices to kill MM cells. Instead, we report, a low Bortezomib concentration, contrary to expectation, achieves severe inhibition of proteasome activity in MM cells: the degree of inhibition exceeds what one would expect from the small proportion of active-sites that Bortezomib inhibits. Our data indicate that Bortezomib achieves this severe inhibition by triggering secondary changes in proteasome structure that further inhibit proteasome activity. Comparing MM cells to other, Bortezomib-resistant, cancer cells shows that the degree of proteasome inhibition is the greatest in MM cells and only there leads to proteasome stress, providing an explanation for why Bortezomib is effective against MM but not other 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.