ArticleCell chemical biology2017
Inhibition of the Proteasome β2 Site Sensitizes Triple-Negative Breast Cancer Cells to β5 Inhibitors and Suppresses Nrf1 Activation.
Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 115 citations in OpenAlex.
- Proteasome inhibition enhances lysosome-mediated targeted protein degradation.Cell death & disease · 2026Article
- α-Aminoboronic Acid Moieties in Boro Dipeptides Modulate Proteasome Subunit Selectivity and Provide Access to Compounds with Potent Anticancer and Anti-Inflammatory Activity.Journal of medicinal chemistry · 2025Article
- Development of Macrocyclic Peptide-Based Proteasome Inhibitors with Enhanced Blood-Brain Barrier Penetration for Treating Brain Neoplasms.Journal of medicinal chemistry · 2025Article
- A new era in cancer therapy: targeting the Proteasome-Bcl-2 axis.Journal of experimental & clinical cancer research : CR · 2025Review
- Proteostasis Disruption by Proteasome Inhibitor MG132 and Propolin G Induces ER Stress- and Autophagy-Mediated Apoptosis in Breast Cancer.Food science & nutrition · 2025Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Suppressing proteasome activity enhances sensitivity to actinomycin D in diffuse anaplastic Wilms tumor.Cell reports. Medicine · 2025Article
- Highly specific Immunoproteasome inhibitor M3258 induces proteotoxic stress and apoptosis in KMT2A::AFF1 driven acute lymphoblastic leukemia.Scientific reports · 2025Article
- All-stage targeted nanodiscs for glioma treatment by inducing cuproptosis and apoptosis of cancer cells and cancer stem cells.Asian journal of pharmaceutical sciences · 2025Article
- Loss of correlated proteasomal subunit expression selectively promotes the 20SCommunications biology · 2025Article
- Association of Proteasome Activity and Pool Heterogeneity with Markers Determining the Molecular Subtypes of Breast Cancer.Cancers · 2025Article
- Proteasome: Role in T Cell Function Regulation.International journal of biological sciences · 2025Review
- Actinomycin D and bortezomib disrupt protein homeostasis in Wilms tumor.bioRxiv : the preprint server for biology · 2024Article
- Inhibition of proteolytic and ATPase activities of the proteasome by the BTK inhibitor CGI-1746.iScience · 2024Article
- HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer.British journal of cancer · 2024Article
- Integrated transcriptomics- and structure-based drug repositioning identifies drugs with proteasome inhibitor properties.Scientific reports · 2024Article
- Multi-omics analysis identifies repurposing bortezomib in the treatment of kidney-, nervous system-, and hematological cancers.Scientific reports · 2024Article
- Understanding the Transcription Factor NFE2L1/NRF1 from the Perspective of Hallmarks of Cancer.Antioxidants (Basel, Switzerland) · 2024Review
- Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer.Cancer research communications · 2024Article
- Article
8 more citing papers are in PubMed but not listed here.
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10 authors at 3 institutions in 2 countries.
Funding
Abstract
The proteasome inhibitors carfilzomib (Cfz) and bortezomib (Btz) are used successfully to treat multiple myeloma, but have not shown clinical efficacy in solid tumors. Here we show that clinically achievable inhibition of the β5 site of the proteasome by Cfz and Btz does not result in loss of viability of triple-negative breast cancer cell lines. We use site-specific inhibitors and CRISPR-mediated genetic inactivation of β1 and β2 to demonstrate that inhibiting a second site of the proteasome, particularly the β2 site, sensitizes cell lines to Btz and Cfz in vitro and in vivo. Inhibiting both β5 and β2 suppresses production of the soluble, active form of the transcription factor Nrf1 and prevents the recovery of proteasome activity through induction of new proteasomes. These findings provide a strong rationale for the development of dual β5 and β2 inhibitors for the treatment of solid tumors.
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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.