ArticleProceedings of the National Academy of Sciences of the United States of America2012
Heat shock protein 90α (HSP90α), a substrate and chaperone of DNA-PK necessary for the apoptotic response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
59 citing papers in PubMed, 83 citations in OpenAlex.
- Envafolimab - novel anti-PD-1/PD-L1 antibody in cancer treatment.Frontiers in immunology · 2026Review
- The Hsp90β Isoform: An Attractive Target for Drug Development.Medicinal research reviews · 2025Review
- RFC1 regulates the expansion of neural progenitors in the developing zebrafish cerebellum.Nature communications · 2025Article
- CD47-blocking antibody confers metabolic benefits against obesity.Cell reports. Medicine · 2025Article
- CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Relevance of Comet Assay and Phosphorylated-Hsp90α in Cancer Patients' Peripheral Blood Leukocytes as Tools to Assess Cisplatin-based Chemotherapy Clinical Response and Disease Outcome.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024Article
- Proteomics Applications inPathogens (Basel, Switzerland) · 2023Review
- Activation of autophagy depends on Atg1/Ulk1-mediated phosphorylation and inhibition of the Hsp90 chaperone machinery.Cell reports · 2023Article
- Role of heat shock protein 90 as an antiviral target for swine enteric coronaviruses.Virus research · 2023Article
- Review
- O-GlcNAcylation suppresses TRAP1 activity and promotes mitochondrial respiration.Cell stress & chaperones · 2022Article
- Cytosolic Hsp90 Isoform-Specific Functions and Clinical Significance.Biomolecules · 2022Review
- Review
- A Novel Role for DNA-PK in Metabolism by Regulating Glycolysis in Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Senolytics: Eliminating Senescent Cells and Alleviating Intervertebral Disc Degeneration.Frontiers in bioengineering and biotechnology · 2022Review
- Ailanthus Altissima-derived Ailanthone enhances Gastric Cancer Cell Apoptosis by Inducing the Repression of Base Excision Repair by Downregulating p23 Expression.International journal of biological sciences · 2021Article
- DNA-PKcs inhibition impairs HDAC6-mediated HSP90 chaperone function on Aurora A and enhances HDACs inhibitor-induced cell killing by increasing mitotic aberrant spindle assembly.Cell cycle (Georgetown, Tex.) · 2021Article
- Post-translational modifications of Hsp90 and translating the chaperone code.The Journal of biological chemistry · 2020Review
- Advances in DNA Repair-Emerging Players in the Arena of Eukaryotic DNA Repair.International journal of molecular sciences · 2020Review
- RETRACTION: The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model.International journal of molecular sciences · 2020Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The "apoptotic ring" is characterized by the phosphorylation of histone H2AX at serine 139 (γ-H2AX) by DNA-dependent protein kinase (DNA-PK). The γ-H2AX apoptotic ring differs from the nuclear foci patterns observed in response to DNA-damaging agents. It contains phosphorylated DNA damage response proteins including activated Chk2, activated ATM, and activated DNA-PK itself but lacks MDC1 and 53BP1, which are required to initiate DNA repair. Because DNA-PK can phosphorylate heat shock protein 90α (HSP90α) in biochemical assays, we investigated whether HSP90α is involved in the apoptotic ring. Here we show that HSP90α is phosphorylated by DNA-PK on threonines 5 and 7 early during apoptosis and that both phosphorylated HSP90α and DNA-PK colocalize in the apoptotic ring. We also show that DNA-PK is a client of HSP90α and that HSP90α is required for full DNA-PK activation, γ-H2AX formation, DNA fragmentation, and apoptotic body formation. In contrast, HSP90 inhibition by geldanamycin markedly enhances TRAIL-induced DNA-PK and H2AX activation. Together, our results reveal that HSP90α is a substrate and chaperone of DNA-PK in the apoptotic response. The response of phosphorylated HSP90α to TRAIL and its localization to the γ-H2AX ring represent epigenetic features of apoptosis that offer insights for studying and monitoring nuclear apoptosis.
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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.