ArticleCell stress & chaperones2004
Downstream caspases are novel targets for the antiapoptotic activity of the molecular chaperone hsp70.
Article in Cell stress & chaperones, 2004. 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, 83 citations in OpenAlex.
- Acupuncture-induced HSP70 upregulation in neuroprotection: mitochondrial and anti-apoptotic mechanisms.American journal of translational research · 2026Review
- Ozone protects against ischemia-reperfusion injury: molecular mechanisms.Frontiers in pharmacology · 2026Review
- Hsp70 Negatively Regulates Autophagy via Governing AMPK Activation, and Dual Hsp70-Autophagy Inhibition Induces Synergetic Cell Death in NSCLC Cells.International journal of molecular sciences · 2024Article
- Autocrine regulation of tumor cell repopulation by Hsp70-HMGB1 alarmin complex.Journal of experimental & clinical cancer research : CR · 2023Article
- Anti-HSP70 alleviates cell migration and proliferation in colorectal cancer cells (CRC) by targeting CXCR4 (in vitro study).Medical oncology (Northwood, London, England) · 2023Article
- Investigation into the communication between unheated and heat-stressed Caenorhabditis elegans via volatile stress signals.Scientific reports · 2023Article
- Ozone protects cardiomyocytes against ischemia/reperfusion injury: Regulating the heat shock protein 70 (HPS70) expression through activating the JAK2/STAT3 Pathway.Bioengineered · 2021Article
- Prevention of High Glucose-Mediated EMT by Inhibition of Hsp70 Chaperone.International journal of molecular sciences · 2021Article
- Inhibition of the Human Hsc70 System by Small Ligands as a Potential Anticancer Approach.Cancers · 2021Article
- Ethanol Enhances Hyperthermia-Induced Cell Death in Human Leukemia Cells.International journal of molecular sciences · 2021Article
- Delivery of functional exogenous proteins by plant-derived vesicles to human cells in vitro.Scientific reports · 2021Article
- Disruption of the Complex between GAPDH and Hsp70 Sensitizes C6 Glioblastoma Cells to Hypoxic Stress.International journal of molecular sciences · 2021Article
- Bcl-2 Associated Athanogene 2 (BAG2) is Associated With Progression and Prognosis of Hepatocellular Carcinoma: A Bioinformatics-Based Analysis.Pathology oncology research : POR · 2021Article
- Biopesticide emamectin benzoate in the liver of male mice: evaluation of oxidative toxicity with stress protein, DNA oxidation, and apoptosis biomarkers.Environmental science and pollution research international · 2020Article
- Pyrrolylquinoxaline-2-One Derivative as a Potent Therapeutic Factor for Brain Trauma Rehabilitation.Pharmaceutics · 2020Article
- Article
- Combination of Anti-Cancer Drugs with Molecular Chaperone Inhibitors.International journal of molecular sciences · 2019Review
- Etoposide-Induced Apoptosis in Cancer Cells Can Be Reinforced by an Uncoupled Link between Hsp70 and Caspase-3.International journal of molecular sciences · 2018Article
- A comparison of cell survival and heat shock protein expression after radiation in normal dermal fibroblasts, microvascular endothelial cells, and different head and neck squamous carcinoma cell lines.Clinical oral investigations · 2018Article
- Molecular Chaperone Hsp70 and Its Constitutively Active Form Hsc70 Play an Indispensable Role During Eye Development of Drosophila melanogaster.Molecular neurobiology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The response of cancer cells to apoptosis-inducing agents can be characterized by 2 opposing factors, the proapoptotic caspase cascade and the antiapoptotic stress protein Hsp70. We show here that these factors interact in U-937 leukemia cells induced to apoptosis with anticancer drugs, etoposide and adriamycin (ADR). The protective effect of Hsp70 was verified using 2 approaches: mild heat stress and transfection-mediated overexpression of the Hsp70 gene. The increase in Hsp70 levels attained by these 2 methods was found to postpone caspase activation for 12-18 hours. An in vitro assay was developed using mouse myeloma NS0/1 cells, which lack the expression of Hsp70. Measurement of DEVD-ase activity in extracts of apoptotic NS0/1 cells incubated with purified Hsp70 showed that Hsp70 reduced caspase activity by up to 50% of its control value in a dose-dependent manner. The hypothesis that the inhibitory effect of Hsp70 on caspase-3/7 activity related to a direct interaction between Hsp70 and the caspases was tested by reciprocal immunoprecipitations and Far-western analyses. These tests were performed with extracts of Hsp70-overexpressing, control, and ADR-treated U-937 cells and using anti-caspase-3, caspase-7, and anti-Hsp70 antibodies, and the data clearly showed that Hsp70 was able to interact with the proforms of these caspases in cell lysates and with reconstituted purified proteins but did not bind the activated forms of either caspase-3 or -7. This association was also corroborated by a novel, enzyme-linked immunosorbent assay-like assay, protein interaction assay, that combined the advantages of immunoprecipitation and immunoblotting in a 96-well microplate-based assay. Thus, Hsp70 may act to suppress caspase-dependent apoptotic signaling through binding the precursor forms of both caspase-3 and caspase-7 and preventing their maturation.
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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.