ArticleBiochemical pharmacology2016
Proteasomal inhibition potentiates drugs targeting DNA topoisomerase II.
Article in Biochemical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Multifaceted Integrated Analysis of CDK1 and TOP2A Signaling Pathways for Multi-Target Therapeutic Intervention in Epithelial Ovarian Cancer.International journal of molecular sciences · 2026Article
- Reduction of DNA Topoisomerase Top2 Reprograms the Epigenetic Landscape and Extends Health and Life Span Across Species.Aging cell · 2025Article
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- DNA damage-induced proteasome phosphorylation controls substrate recognition and facilitates DNA repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- MG132 dramatically reduces SAA expression in chicken hepatocellular carcinoma cells at the transcript level independent of its endogenous promoter.Molecular biology reports · 2024Article
- The Bisdioxopiperazine ICRF-193 Attenuates LPS-induced IL-1β Secretion by Macrophages.Inflammation · 2024Article
- MDM2 provides TOP2 poison resistance by promoting proteolysis of TOP2βcc in a p53-independent manner.Cell death & disease · 2024Article
- Enzymatic Processing of DNA-Protein Crosslinks.Genes · 2024Review
- Comprehensive Profiling and Therapeutic Insights into Differentially Expressed Genes in Hepatocellular Carcinoma.Cancers · 2023Article
- DNA-PK inhibition extends the therapeutic effects of Top2 poisoning to non-proliferating cells, increasing activity at a cost.Scientific reports · 2023Article
- Genome-Wide CRISPR Screens Reveal ZATT as a Synthetic Lethal Target of TOP2-Poison Etoposide That Can Act in a TDP2-Independent Pathway.International journal of molecular sciences · 2023Article
- ATM inhibitor KU60019 synergistically sensitizes lung cancer cells to topoisomerase II poisons by multiple mechanisms.Scientific reports · 2023Article
- DNA fragility at theOpen biology · 2023Review
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Article
- The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the activity of topoisomerase II during productive infection.PLoS pathogens · 2021Article
- Regulation of topoisomerase II stability and activity by ubiquitination and SUMOylation: clinical implications for cancer chemotherapy.Molecular biology reports · 2021Review
- A Role for VCP/p97 in the Processing of Drug-Stabilized TOP2-DNA Covalent Complexes.Molecular pharmacology · 2021Article
- Debulking of topoisomerase DNA-protein crosslinks (TOP-DPC) by the proteasome, non-proteasomal and non-proteolytic pathways.DNA repair · 2020Review
- Small Molecule Inhibitors Confirm Ubiquitin-Dependent Removal of TOP2-DNA Covalent Complexes.Molecular pharmacology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The reaction mechanism of DNA topoisomerase II (TOP2) involves a covalent double-strand break intermediate in which the enzyme is coupled to DNA via a 5'-phosphotyrosyl bond. This normally transient enzyme-bridged break is stabilised by drugs such as mitoxantrone, mAMSA, etoposide, doxorubicin, epirubicin and idarubicin, which are referred to as TOP2 poisons. Removal of topoisomerase II by the proteasome is involved in the repair of these lesions. In K562 cells, inhibiting the proteasome with MG132 significantly potentiated the growth inhibition by these six drugs that target topoisomerase II, and the highest level of potentiation was observed with mitoxantrone. Mitoxantrone also showed the greatest potentiation by MG132 in three Nalm 6 cell lines with differing levels of TOP2A or TOP2B. Mitoxantrone was also potentiated by the clinically used proteasome inhibitor PS341 (Velcade). We have also shown that proteasome inhibition with MG132 in K562 cells reduces the rate of removal of mitoxantrone or etoposide stabilised topoisomerase complexes from DNA, suggesting a possible mechanism for the potentiation of topoisomerase II drugs by proteasomal inhibition.
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