ArticleThe Journal of biological chemistry2011
Phosphorylation and stabilization of topoisomerase IIα protein by p38γ mitogen-activated protein kinase sensitize breast cancer cells to its poisons.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Hepatic p38γ exacerbates acetaminophen‑induced acute liver injury via PI3K/Akt‑dependent mechanisms.International journal of molecular medicine · 2026Article
- Complex mechanisms of topoisomerase II poisons revealed by whole-genome analysis.Communications biology · 2026Article
- Targeting p38γ synergistically enhances sorafenib-induced cytotoxicity in hepatocellular carcinoma.Cell biology and toxicology · 2025Article
- Protein tyrosine phosphatase PTPH1 potentiates receptor tyrosine kinase HER2 oncogenesis via a PDZ-coupled and phosphorylation-driven scaffold.American journal of cancer research · 2024Article
- Phosphorylation of cell cycle and apoptosis regulatory protein-1 by stress activated protein kinase P38γ is a novel mechanism of apoptosis signaling by genotoxic chemotherapy.Frontiers in oncology · 2024Article
- Review
- New Biomarkers and Treatment Advances in Triple-Negative Breast Cancer.Diagnostics (Basel, Switzerland) · 2023Review
- Regulation of the mitotic chromosome folding machines.The Biochemical journal · 2022Article
- The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer.International journal of molecular sciences · 2021Review
- Exploration of the Role of the C-Terminal Domain of Human DNA Topoisomerase IIα in Catalytic Activity.ACS omega · 2021Article
- The Role of p38γ in Cancer: From review to outlook.International journal of biological sciences · 2021Review
- Multiomics Reveals Ectopic ATP Synthase Blockade Induces Cancer Cell Death via a lncRNA-mediated Phospho-signaling Network.Molecular & cellular proteomics : MCP · 2020Article
- 3,6-Disubstituted 1,2,4-Triazolo[3,4-OncoTargets and therapy · 2020Article
- The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy.Acta pharmaceutica Sinica. B · 2018Review
- Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain.Scientific reports · 2018Article
- The C-terminal 20 Amino Acids of Drosophila Topoisomerase 2 Are Required for Binding to a BRCA1 C Terminus (BRCT) Domain-containing Protein, Mus101, and Fidelity of DNA Segregation.The Journal of biological chemistry · 2016Article
- Review
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer drugs suppress tumor cell growth by inhibiting specific cellular targets. However, most drugs also activate several cellular nonspecific stress pathways, and the implications of these off-target effects are mostly unknown. Here, we report that p38γ, but not p38α, MAPK is specifically activated by treatment of breast cancer cells with topoisomerase II (Topo II) drugs, whereas paclitaxel (Taxol) does not have this effect. The activated p38γ in turn phosphorylates and stabilizes Topo IIα protein, and this enhances the growth inhibition by Topo II drugs. Moreover, p38γ activity was shown to be necessary and sufficient for Topo IIα expression, the drug-p38γ-Topo IIα axis is only detected in intrinsically sensitive but not resistant cells, and p38γ is co-overexpressed with Topo IIα protein in primary breast cancers. These results reveal a new paradigm in which p38γ actively regulates the drug-Topo IIα signal transduction, and this may be exploited to increase the therapeutic activity of Topo II drugs.
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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.