ArticleAmerican journal of physiology. Heart and circulatory physiology2008
A therapeutic dose of doxorubicin activates ubiquitin-proteasome system-mediated proteolysis by acting on both the ubiquitination apparatus and proteasome.
Article in American journal of physiology. Heart and circulatory physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 91 citations in OpenAlex.
- The Transcription Axes ERK-Elk1, JNK-cJun, and JAK-STAT Promote Autophagy Activation and Proteasome Inhibitor Resistance in Prostate Cancer Cells.Current issues in molecular biology · 2025Article
- Anthracyclines disaggregate and restore mutant p63 function: a potential therapeutic approach for AEC syndrome.Cell death discovery · 2025Article
- Diacylglycerol Kinase ζ Attenuates Doxorubicin-Induced Cardiotoxicity Through p53 Degradation.Journal of the American Heart Association · 2025Article
- Exploring Anthracycline-Induced Cardiotoxicity from the Perspective of Protein Quality Control.Reviews in cardiovascular medicine · 2024Review
- Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors.Cell communication and signaling : CCS · 2024Review
- DoxoDB: A Database for the Expression Analysis of Doxorubicin-Induced lncRNA Genes.Non-coding RNA · 2023Article
- Cardiac Molecular Remodeling by Anticancer Drugs: Doxorubicin Affects More Metabolism While Mitoxantrone Impacts More Autophagy in Adult CD-1 Male Mice.Biomolecules · 2023Article
- Cellular Mechanisms Mediating Exercise-Induced Protection against Cardiotoxic Anthracycline Cancer Therapy.Cells · 2023Review
- Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play.Frontiers in cardiovascular medicine · 2023Review
- Formoterol reduces muscle wasting in mice undergoing doxorubicin chemotherapy.Frontiers in oncology · 2023Article
- Article
- Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α.Cell death & disease · 2022Article
- Transcriptome-wide association study uncovers the role of essential genes in anthracycline-induced cardiotoxicity.NPJ genomic medicine · 2021Article
- Consideration of Sex as a Biological Variable in the Development of Doxorubicin Myotoxicity and the Efficacy of Exercise as a Therapeutic Intervention.Antioxidants (Basel, Switzerland) · 2021Review
- A Hyperactive Kunjin Virus NS3 Helicase Mutant Demonstrates Increased Dissemination and Mortality in Mosquitoes.Journal of virology · 2020Article
- Self-Propelling Targeted Magneto-Nanobots for Deep Tumor Penetration and pH-Responsive Intracellular Drug Delivery.Scientific reports · 2020Article
- Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside.Frontiers in cardiovascular medicine · 2020Review
- Prokineticin Receptor-1 Signaling Inhibits Dose- and Time-Dependent Anthracycline-Induced Cardiovascular Toxicity Via Myocardial and Vascular Protection.JACC. CardioOncology · 2019Article
- Suppression of the Ubiquitin Pathway by Small Molecule Binding to Ubiquitin Enhances Doxorubicin Sensitivity of the Cancer Cells.Molecules (Basel, Switzerland) · 2019Article
- Therapeutic doses of doxorubicin induce premature senescence of human mesenchymal stem cells derived from menstrual blood, bone marrow and adipose tissue.International journal of hematology · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The ubiquitin proteasome system (UPS) degrades abnormal proteins and most unneeded normal proteins, thereby playing a critical role in protein homeostasis in the cell. Proteasome inhibition is effective in treating certain forms of cancer, while UPS dysfunction is increasingly implicated in the pathogenesis of many severe and yet common diseases. It has been previously shown that doxorubicin (Dox) enhances the degradation of a UPS surrogate substrate in mouse hearts. To address the underlying mechanism, in the present study, we report that 1) Dox not only enhances the degradation of an exogenous UPS reporter (GFPu) but also antagonizes the proteasome inhibitor-induced accumulation of endogenous substrates (e.g., beta-catenin and c-Jun) of the UPS in cultured NIH 3T3 cells and cardiomyocytes; 2) Dox facilitates the in vitro degradation of GFPu and c-Jun by the reconstituted UPS via the enhancement of proteasomal function; 3) Dox at a therapeutically relevant dose directly stimulates the peptidase activities of purified 20S proteasomes; and 4) Dox increases, whereas proteasome inhibition decreases, E3 ligase COOH-terminus of heat shock protein cognate 70 in 3T3 cells via a posttranscriptional mechanism. These new findings suggest that Dox activates the UPS by acting directly on both the ubiquitination apparatus and proteasome.
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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.