ArticleMolecular therapy oncolytics2020
Inhibition of USP14 Deubiquitinating Activity as a Potential Therapy for Tumors with
Article in Molecular therapy oncolytics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- TMEM158-mediated TGF-β signaling pathway modulates the sensitivity of TP53-deficient osteosarcoma to USP14 inhibitors.Molecular and cellular biochemistry · 2026Article
- COPS5 inhibition synergizes with the antitumor effect of trastuzumab by PTEN upregulation in HER2-amplified gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Loss of the proteasomal deubiquitinase USP14 induces growth defects and a senescence phenotype in colorectal cancer cells.Scientific reports · 2024Article
- Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.Acta pharmacologica Sinica · 2023Article
- DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases.Biomolecules · 2023Review
- Review
- Targeting ubiquitin specific proteases (USPs) in cancer immunotherapy: from basic research to preclinical application.Journal of experimental & clinical cancer research : CR · 2023Review
- Proliferation and migration of ML1 follicular thyroid cancer cells are inhibited by IU1 targeting USP14: role of proteasome and autophagy flux.Frontiers in cell and developmental biology · 2023Article
- USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer.Nature communications · 2022Article
- Pro-apoptotic and anti-apoptotic regulation mediated by deubiquitinating enzymes.Cellular and molecular life sciences : CMLS · 2022Review
- Protein clearance strategies for disease intervention.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
- USP14 Regulates Cancer Cell Growth in a Fatty Acid Synthase-Independent Manner.International journal of molecular sciences · 2021Article
- PR-619, a General Inhibitor of Deubiquitylating Enzymes, Diminishes Cisplatin Resistance in Urothelial Carcinoma Cells through the Suppression of c-Myc: An In Vitro and In Vivo Study.International journal of molecular sciences · 2021Article
- Deubiquitinases in hematological malignancies.Biomarker research · 2021Review
- LncRNA CASC2 inhibits lung adenocarcinoma progression through forming feedback loop with miR-21/p53 axis.The Kaohsiung journal of medical sciences · 2021Article
- Small-Molecule Inhibitors Targeting Proteasome-Associated Deubiquitinases.International journal of molecular sciences · 2021Review
- Deubiquitinases: Modulators of Different Types of Regulated Cell Death.International journal of molecular sciences · 2021Review
- MicroRNA-497-5p Is Downregulated in Hepatocellular Carcinoma and Associated with Tumorigenesis and Poor Prognosis in Patients.International journal of genomics · 2021Article
- Regulation of NFκB Signalling by Ubiquitination: A Potential Therapeutic Target in Head and Neck Squamous Cell Carcinoma?Cancers · 2020Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Functional elimination of p53 is a common feature of a large percentage of human malignancies. Here, we report the development of a pharmacological strategy aimed at restoring p53 function and its use for targeted therapy in p53-deficient mice. Specific inhibition of deubiquitinases ubiquitin-specific peptidase 14 (USP14) resulted in durable tumor regressions of autochthonous lymphomas and sarcomas in p53-deficient mice without affecting normal tissues, and therapeutic response was correlated with an increase in the ubiquitination of constitutive photomorphogenesis 9 (COP9) signalosome subunit 5 (COPS5), a key negative regulatory effector for p53. Inhibition of USP14 resulted in durable tumor regression through COPS5 deubiquitilation and a p53-dependent and -independent regulation mechanism by USP14. This series highlights the utility of proteasome deubiquitinating activity inhibition as a novel treatment paradigm for p53-deficient cancers. In addition, it provides preliminary evidence that inhibition of USP14 resulted in durable tumor regression through COPS5 deubiquitilation and p53-dependent and -independent regulation mechanism by USP14. These findings suggest that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target for patients with p53 deficiency.
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