ArticleOncotarget2016
TNF induced cleavage of HSP90 by cathepsin D potentiates apoptotic cell death.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Intracellular Staphylococcus aureus triggers isolate-specific host transcriptional responses alongside TNF-R1 regulated cell fate decisions.Cell communication and signaling : CCS · 2026Article
- Loss of ADAM15 prevents necroptosis induction by partial RIPK1 degradation due to enhanced TNF-R1 surface expression and basal caspase-8 activation.Cell communication and signaling : CCS · 2025Article
- Cathepsin D promotes acute myeloid leukemia progression through stabilization of the anti-apoptotic proteins.Cell death & disease · 2025Article
- Low-density lipoprotein receptor-related protein 6 ameliorates cardiac hypertrophy by regulating CTSD/HSP90α signaling during pressure overload.Acta pharmacologica Sinica · 2025Article
- Molecular Insights into the Interaction of Cathepsin D and Iron in Chronic Wound Healing: Exploring Therapeutic Potential and Mechanisms.Biomedicines · 2025Article
- The Effect of 7-Day Cold Water Acclimation on Autophagic and Apoptotic Responses in Young Males.Advanced biology · 2025Article
- ABT199/venetoclax synergism with thiotepa enhances the cytotoxicity of fludarabine, cladribine and busulfan in AML cells.Oncotarget · 2024Article
- Contribution of HSP90 Cleavage to the Cytotoxic Effect of Suberoylanilide Hydroxamic AcidBiomolecules & therapeutics · 2024Article
- Role of heat shock protein 90 as an antiviral target for swine enteric coronaviruses.Virus research · 2023Article
- Hsp90 as a Myokine: Its Association with Systemic Inflammation after Exercise Interventions in Patients with Myositis and Healthy Subjects.International journal of molecular sciences · 2022Article
- Expression of CD70 Modulates Nitric Oxide and Redox Status in Endothelial Cells.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Cathepsin D as a potential therapeutic target to enhance anticancer drug-induced apoptosis via RNF183-mediated destabilization of Bcl-xL in cancer cells.Cell death & disease · 2022Article
- Cathepsin D deficiency in mammary epithelium transiently stalls breast cancer by interference with mTORC1 signaling.Nature communications · 2020Article
- Synergistic Anti Leukemia Effect of a Novel Hsp90 and a Pan Cyclin Dependent Kinase Inhibitors.Molecules (Basel, Switzerland) · 2020Article
- The dual functions of α-tubulin acetylation in cellular apoptosis and autophage induced by tanespimycin in lung cancer cells.Cancer cell international · 2020Article
- Unraveling oxidative stress response in the cestode parasite Echinococcus granulosus.Scientific reports · 2019Article
- Traditional and Novel Mechanisms of Heat Shock Protein 90 (HSP90) Inhibition in Cancer Chemotherapy Including HSP90 Cleavage.Biomolecules & therapeutics · 2019Article
- Palmitoylation is required for TNF-R1 signaling.Cell communication and signaling : CCS · 2019Article
- 'Patchiness' and basic cancer research: unravelling the proteases.Cell cycle (Georgetown, Tex.) · 2019Review
- Lysosomal cathepsin D is upregulated in Alzheimer's disease neocortex and may be a marker for neurofibrillary degeneration.Brain pathology (Zurich, Switzerland) · 2019Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During apoptosis induction by TNF, the extrinsic and intrinsic apoptosis pathways converge at the lysosomal-mitochondrial interface. Earlier studies showed that the lysosomal aspartic protease Cathepsin D (CtsD) cleaves Bid to tBid, resulting in the amplification of the initial apoptotic cascade via mitochondrial outer membrane permeabilization (MOMP).The goal of this study was to identify further targets for CtsD that might be involved in activation upon death receptor ligation. Using a proteomics screen, we identified the heat shock protein 90 (HSP90) to be cleaved by CtsD after stimulation of U937 or other cell lines with TNF, FasL and TRAIL. HSP90 cleavage corresponded to apoptosis sensitivity of the cell lines to the different stimuli. After mutation of the cleavage site, HSP90 partially prevented apoptosis induction in U937 and Jurkat cells. Overexpression of the cleavage fragments in U937 and Jurkat cells showed no effect on apoptosis, excluding a direct pro-apoptotic function of these fragments. Pharmacological inhibition of HSP90 with 17AAG boosted ligand mediated apoptosis by enhancing Bid cleavage and caspase-9 activation. Together, we demonstrated that HSP90 plays an anti-apoptotic role in death receptor signalling and that CtsD-mediated cleavage of HSP90 sensitizes cells for apoptosis. These findings identify HSP90 as a potential target for cancer therapy in combination with death ligands (e.g. TNF or TRAIL).
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Registered trials
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