ArticlePloS one2012
Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 67 citations in OpenAlex.
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- A lysis-derived PMSF and orthovanadate oxidant defines a distinct cysteine-engagement profile.Cell chemical biology · 2026Article
- Short-Term Exposure to a 50 Hz Extremely Low-Frequency Electromagnetic Field (ELF-EMF) Leads to ROS-Mediated DNA Damage in Gynecological and Urological Cancer CellsInternational journal of molecular sciences · 2026Article
- Positive Effects of Allicin on Cytotoxicity, Antioxidative Status, and Immunity in "Antioxidants (Basel, Switzerland) · 2026Article
- Targeting proteostasis pathways for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- Contribution of HSP90 Cleavage to the Cytotoxic Effect of Suberoylanilide Hydroxamic AcidBiomolecules & therapeutics · 2024Article
- TRPA1 activation and Hsp90 inhibition synergistically downregulate macrophage activation and inflammatory responses in vitro.BMC immunology · 2023Article
- Anti-dermatophytic activity of cold atmospheric plasma against Trichophyton rubrum via affecting fungal growth, morphology, drug susceptibility and HSP90 gene expression.Scientific reports · 2022Article
- Interchangeable utilization of metals: New perspectives on the impacts of metal ions employed in ancient and extant biomolecules.The Journal of biological chemistry · 2021Review
- Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice.International journal of molecular sciences · 2021Article
- Implications of Iron Deficiency in STEMI Patients and in a Murine Model of Myocardial Infarction.JACC. Basic to translational science · 2021Article
- Cleavage of HSP90β induced by histone deacetylase inhibitor and proteasome inhibitor modulates cell growth and apoptosis.Cell stress & chaperones · 2021Article
- DRP1 promotes lactate utilization in KRAS-mutant non-small-cell lung cancer cells.Cancer science · 2020Article
- In Vitro Inhibition of Hsp90 Protein by Benzothiazoloquinazolinequinones Is Enhanced in The Presence of Ascorbate. A Preliminary In Vivo Antiproliferative Study.Molecules (Basel, Switzerland) · 2020Article
- The HSP90 inhibitor onalespib potentiates 177Lu‑DOTATATE therapy in neuroendocrine tumor cells.International journal of oncology · 2019Article
- Traditional and Novel Mechanisms of Heat Shock Protein 90 (HSP90) Inhibition in Cancer Chemotherapy Including HSP90 Cleavage.Biomolecules & therapeutics · 2019Article
- MicroRNA-126 regulates Hypoxia-Inducible Factor-1α which inhibited migration, proliferation, and angiogenesis in replicative endothelial senescence.Scientific reports · 2019Article
- Physical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone.Scientific reports · 2019Article
- Non-enzymatic cleavage of Hsp90 by oxidative stress leads to actin aggregate formation: A novel gain-of-function mechanism.Redox biology · 2019Article
- Drug-Induced HSP90 Inhibition Alleviates Pain in Monoarthritic Rats and Alters the Expression of New Putative Pain Players at the DRG.Molecular neurobiology · 2018Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hsp90 is an essential chaperone that is necessary for the folding, stability and activity of numerous proteins. In this study, we demonstrate that free radicals formed during oxidative stress conditions can cleave Hsp90. This cleavage occurs through a Fenton reaction which requires the presence of redox-active iron. As a result of the cleavage, we observed a disruption of the chaperoning function of Hsp90 and the degradation of its client proteins, for example, Bcr-Abl, RIP, c-Raf, NEMO and hTert. Formation of Hsp90 protein radicals on exposure to oxidative stress was confirmed by immuno-spin trapping. Using a proteomic analysis, we determined that the cleavage occurs in a conserved motif of the N-terminal nucleotide binding site, between Ile-126 and Gly-127 in Hsp90β, and between Ile-131 and Gly-132 in Hsp90α. Given the importance of Hsp90 in diverse biological functions, these findings shed new light on how oxidative stress can affect cellular homeostasis.
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