ArticleThe Journal of biological chemistry2016
The Deubiquitinase Inhibitor PR-619 Sensitizes Normal Human Fibroblasts to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-mediated Cell Death.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Post-Translational Modifications in Cancer-Associated CD8⁺ T-Cell Exhaustion: Mechanisms and Therapeutic Opportunities.International journal of biological sciences · 2026Review
- TRAIL and its receptors in cardiac diseases.Frontiers in physiology · 2023Review
- Regulation of Cancer Metabolism by Deubiquitinating Enzymes: The Warburg Effect.International journal of molecular sciences · 2021Review
- A Dual Role for Death Receptor 5 in Regulating Cardiac Fibroblast Function.Frontiers in cardiovascular medicine · 2021Article
- Inhibition of deubiquitination by PR-619 induces apoptosis and autophagy via ubi-protein aggregation-activated ER stress in oesophageal squamous cell carcinoma.Cell proliferation · 2021Article
- Targeting apoptosis in cancer therapy.Nature reviews. Clinical oncology · 2020Review
- TRAIL signals, extracellular matrix and vessel remodelling.Vascular biology (Bristol, England) · 2020Review
- The Deubiquitinating Enzyme Inhibitor PR-619 is a Potent DNA Topoisomerase II Poison.Molecular pharmacology · 2019Article
- Death receptor 5 contributes to cardiomyocyte hypertrophy through epidermal growth factor receptor transactivation.Journal of molecular and cellular cardiology · 2019Article
- MEDI3039, a novel highly potent tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 2 agonist, causes regression of orthotopic tumors and inhibits outgrowth of metastatic triple-negative breast cancer.Breast cancer research : BCR · 2019Article
- Eukaryotic initiation factor 5B (eIF5B) provides a critical cell survival switch to glioblastoma cells via regulation of apoptosis.Cell death & disease · 2019Article
- Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation.Nature communications · 2018Article
- TRAIL pathway targeting therapeutics.Expert review of precision medicine and drug development · 2018Article
- The proteasome deubiquitinase inhibitor b-AP15 enhances DR5 activation-induced apoptosis through stabilizing DR5.Scientific reports · 2017Article
- Andrographolide sensitizes prostate cancer cells to TRAIL-induced apoptosis.Asian journal of andrologyArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
TNF-related apoptosis-inducing ligand (TRAIL) is a potential cancer therapy that selectively targets cancer cell death while non-malignant cells remain viable. Using a panel of normal human fibroblasts, we characterized molecular differences in human foreskin fibroblasts and WI-38 TRAIL-resistant cells and marginally sensitive MRC-5 cells compared with TRAIL-sensitive human lung and colon cancer cells. We identified decreased caspase-8 protein expression and protein stability in normal fibroblasts compared with cancer cells. Additionally, normal fibroblasts had incomplete TRAIL-induced caspase-8 activation compared with cancer cells. We found that normal fibroblasts lack the ubiquitin modification of caspase-8 required for complete caspase-8 activation. Treatment with the deubiquitinase inhibitor PR-619 increased caspase-8 ubiquitination and caspase-8 enzymatic activity and sensitized normal fibroblasts to TRAIL-mediated apoptosis. Therefore, posttranslational regulation of caspase-8 confers resistance to TRAIL-induced cell death in normal cells through blockade of initiation of the extrinsic cell death pathway.
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Registered trials
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