ArticlePloS one2016
LEDGF/p75 Overexpression Attenuates Oxidative Stress-Induced Necrosis and Upregulates the Oxidoreductase ERP57/PDIA3/GRP58 in Prostate Cancer.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Peptide Loading Complex in Cancer: From Peptide Translocation, Editing, and Loading into MHC-I to a Potential Therapeutic Target.Current medical science · 2026Review
- Article
- Review
- PSIP1/LEDGF reduces R-loops at transcription sites to maintain genome integrity.Nature communications · 2024Article
- Article
- Relationship Between Anti-DFS70 Autoantibodies and Oxidative Stress.Biomarker insights · 2022Article
- Article
- LEDGINs, Inhibitors of the Interaction Between HIV-1 Integrase and LEDGF/p75, Are Potent Antivirals with a Potential to Cure HIV Infection.Advances in experimental medicine and biology · 2021Article
- Impairment of cell adhesion and migration by inhibition of protein disulphide isomerases in three breast cancer cell lines.Bioscience reports · 2020Article
- Impact of Androgen Deprivation on Oxidative Stress and Antioxidant Status in Nigerian Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy.JCO global oncology · 2020Article
- Targeting epigenetic protein-protein interactions with small-molecule inhibitors.Future medicinal chemistry · 2020Review
- Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions.Auto- immunity highlights · 2020Review
- Insight in HIV Integration Site Selection Provides a Block-and-Lock Strategy for a Functional Cure of HIV Infection.Viruses · 2018Review
- Protective effect of docosahexaenoic acid on lipotoxicity-mediated cell death in Schwann cells: Implication of PI3K/AKT and mTORC2 pathways.Brain and behavior · 2018Article
- Glucocorticoids Induce Stress Oncoproteins Associated with Therapy-Resistance in African American and European American Prostate Cancer Cells.Scientific reports · 2018Article
- Article
- Microenvironment-Cell Nucleus Relationship in the Context of Oxidative Stress.Frontiers in cell and developmental biology · 2018Review
- Oxidative stress and prostatic diseases.Molecular and clinical oncology · 2017Article
- Analysis of STAT3 post-translational modifications (PTMs) in human prostate cancer with different Gleason Score.Oncotarget · 2017Article
- Writing, erasing and reading histone lysine methylations.Experimental & molecular medicine · 2017Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Prostate cancer (PCa) mortality is driven by highly aggressive tumors characterized by metastasis and resistance to therapy, and this aggressiveness is mediated by numerous factors, including activation of stress survival pathways in the pro-inflammatory tumor microenvironment. LEDGF/p75, also known as the DFS70 autoantigen, is a stress transcription co-activator implicated in cancer, HIV-AIDS, and autoimmunity. This protein is targeted by autoantibodies in certain subsets of patients with PCa and inflammatory conditions, as well as in some apparently healthy individuals. LEDGF/p75 is overexpressed in PCa and other cancers, and promotes resistance to chemotherapy-induced cell death via the transactivation of survival proteins. We report in this study that overexpression of LEDGF/p75 in PCa cells attenuates oxidative stress-induced necrosis but not staurosporine-induced apoptosis. This finding was consistent with the observation that while LEDGF/p75 was robustly cleaved in apoptotic cells into a p65 fragment that lacks stress survival activity, it remained relatively intact in necrotic cells. Overexpression of LEDGF/p75 in PCa cells led to the upregulation of transcript and protein levels of the thiol-oxidoreductase ERp57 (also known as GRP58 and PDIA3), whereas its depletion led to ERp57 transcript downregulation. Chromatin immunoprecipitation and transcription reporter assays showed LEDGF/p75 binding to and transactivating the ERp57 promoter, respectively. Immunohistochemical analysis revealed significantly elevated co-expression of these two proteins in clinical prostate tumor tissues. Our results suggest that LEDGF/p75 is not an inhibitor of apoptosis but rather an antagonist of oxidative stress-induced necrosis, and that its overexpression in PCa leads to ERp57 upregulation. These findings are of significance in clarifying the role of the LEDGF/p75 stress survival pathway in PCa.
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Registered trials
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