ArticleOncotarget2019
Tumor necrosis factor related apoptosis inducing ligand (TRAIL) regulates deubiquitinase USP5 in tumor cells.
Article in Oncotarget, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- TRAIL-resistant glioma cells resist Withania somnifera mediated apoptosis via USP5 upregulation.Scientific reports · 2025Article
- USP5 knockdown alleviates lung cancer progression via activating PARP1-mediated mTOR signaling pathway.Biology direct · 2023Article
- Ubiquitin receptors play redundant roles in the proteasomal degradation of the p53 repressor MDM2.FEBS letters · 2022Article
- On the Study of Deubiquitinases: Using the Right Tools for the Job.Biomolecules · 2022Review
- The Next Frontier: Translational Development of Ubiquitination, SUMOylation, and NEDDylation in Cancer.International journal of molecular sciences · 2022Review
- Deubiquitinases: Modulators of Different Types of Regulated Cell Death.International journal of molecular sciences · 2021Review
- Lestaurtinib potentiates TRAIL-induced apoptosis in glioma via CHOP-dependent DR5 induction.Journal of cellular and molecular medicine · 2020Article
- Role of Deubiquitinases in Human Cancers: Potential Targeted Therapy.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway has emerged as a cancer therapeutic target. However, clinical trials have proven that most human cancers are resistant to TRAIL. We show that exposure to recombinant TRAIL resulted in the accumulation of ubiquitinated proteins and free ubiquitin polymers, suggesting a link between TRAIL and the ubiquitin (Ub)-proteasome pathway. TRAIL treatment in cancer cells reduced the activity and cleavage of USP5, a deubiquitinase (DUB) previously shown to target unanchored Ub polymers and regulate p53-mediated transcription. TRAIL was effective in suppressing USP5 activity and cleavage in TRAIL-sensitive cells but not resistant cells. Knockdown of USP5 in TRAIL-resistant cells demonstrated that USP5 controls apoptotic responsiveness to TRAIL. USP5 cleavage and ubiquitination were blocked by caspase-8 specific inhibitors. A small-molecule USP5/9× inhibitor (G9) combined with TRAIL enhanced apoptosis and blocked colony growth in highly TRAIL-resistant cell lines. Finally, USP5 protein levels and activity were found to be frequently deregulated in TRAIL-resistant cells. Together, we conclude that activated TRAIL enhances USP5 activity and induces apoptosis in TRAIL-sensitive and -resistant cells. We also suggest that USP5 inhibition may be effective in inducing apoptotic thresholds to enhance responsiveness to TRAIL.
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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.