ArticleBlood2014
A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06536413 (Phase IB/II Study Combining All-Trans Retinoic Acid), which is not on this map. Cited by 204 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Phase IB/II Study Combining All-Trans Retinoic Acid (ATRA) With Carfilzomib Based Therapy in Plasma Cell Myeloma Patients Refractory to Carfilzomib
Who cites it
204 citing papers in PubMed, 2 syntheses or guidelines pooled it, 310 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases.Frontiers in physiology · 2020Pooled it
- Positive cytoplasmic UCHL5 tumor expression in gastric cancer is linked to improved prognosis.PloS one · 2018Trial
- USP7 inhibits FOXO1 activity in chronic lymphocytic leukaemia cells enhancing cell survival.Molecular oncology · 2026Article
- Substrate biasing in UCHL5 proteoforms.bioRxiv : the preprint server for biology · 2026Article
- Emerging regulatory model of Ubiquitin-Specific Proteases 14 in cancer: from canonical oncogenesis to TME modulation, therapeutic resistance, and non-canonical activities.Journal of translational medicine · 2026Review
- Deubiquitinating enzymes-mediated post-translational modifications of ferroptosis regulates cancer drug resistance.Discover oncology · 2026Review
- Proteomic profiling revealed unique disease biology associated with 1q abnormalities in multiple myeloma.NPJ precision oncology · 2026Article
- The 19S proteasome as a therapeutic target in hematologic malignancies.Frontiers in cell and developmental biology · 2026Review
- Targeting ubiquitin-specific protease 14 reduces metastatic potential and metabolic activity in cervical cancer via direct modulation of monocarboxylate transporter-4.Journal of translational medicine · 2025Article
- Identification of AKOS, a Chikungunya virus inhibitor, as a USP14 inhibitor for colorectal cancer treatment.Acta pharmacologica Sinica · 2025Article
- USP14 and UCHL5 synergistically deubiquitinate PKCα and translocate NF-κB to promote the progression of anaplastic thyroid cancer.Cell death & disease · 2025Article
- Article
- Proteostasis Disruption by Proteasome Inhibitor MG132 and Propolin G Induces ER Stress- and Autophagy-Mediated Apoptosis in Breast Cancer.Food science & nutrition · 2025Article
- Effect of deubiquitinases in head and neck squamous cell carcinoma (Review).Oncology letters · 2025Review
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- Article
- Oncogenic and immunological functions of USP35 in pan-cancer and its potential as a biomarker in kidney clear cell carcinoma.BMC cancer · 2025Article
- Insights into Free Drug Release from EfficaciousACS chemical biology · 2025Article
- A novel USP4 inhibitor that suppresses colorectal cancer stemness by promoting β-catenin and Twist1 degradation.Journal of translational medicine · 2025Article
144 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Proteasome inhibitors have demonstrated that targeting protein degradation is effective therapy in multiple myeloma (MM). Here we show that deubiquitylating enzymes (DUBs) USP14 and UCHL5 are more highly expressed in MM cells than in normal plasma cells. USP14 and UCHL5 short interfering RNA knockdown decreases MM cell viability. A novel 19S regulatory particle inhibitor b-AP15 selectively blocks deubiquitylating activity of USP14 and UCHL5 without inhibiting proteasome activity. b-AP15 decreases viability in MM cell lines and patient MM cells, inhibits proliferation of MM cells even in the presence of bone marrow stroma cells, and overcomes bortezomib resistance. Anti-MM activity of b-AP15 is associated with growth arrest via downregulation of CDC25C, CDC2, and cyclin B1 as well as induction of caspase-dependent apoptosis and activation of unfolded protein response. In vivo studies using distinct human MM xenograft models show that b-AP15 is well tolerated, inhibits tumor growth, and prolongs survival. Combining b-AP15 with suberoylanilide hydroxamic acid, lenalidomide, or dexamethasone induces synergistic anti-MM activity. Our preclinical data showing efficacy of b-AP15 in MM disease models validates targeting DUBs in the ubiquitin proteasomal cascade to overcome proteasome inhibitor resistance and provides the framework for clinical evaluation of USP14/UCHL5 inhibitors to improve patient outcome in MM.
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What OpenQuestion holds
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.