ArticleCell death & disease2013
Valosin-containing protein regulates the proteasome-mediated degradation of DNA-PKcs in glioma cells.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
28 citing papers in PubMed, 43 citations in OpenAlex.
- VCP at the crossroads of UPS and autophagy in cancer.Genes & diseases · 2027Review
- Valosin-Containing Protein (VCP)/p97 Expression Correlation of Prognosis of Clear Cell Renal Cell Carcinomas.Biomedicines · 2026Article
- Article
- Review
- Salt-inducible kinase 2 confers radioresistance in colorectal cancer by facilitating homologous recombination repair.MedComm · 2025Article
- The prognostic value and biological significance of MRI CE-T1-based radiomics models in CNS5-identified GBM: a multi-center study.Scientific reports · 2024Article
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- rAAV capsid mutants eliminate leaky expression from DNA donor template for homologous recombination.Nucleic acids research · 2024Article
- Valosin-Containing Protein (VCP): A Review of Its Diverse Molecular Functions and Clinical Phenotypes.International journal of molecular sciences · 2024Review
- An exosome mRNA-related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinoma.BMC medical genomics · 2024Article
- Topoisomerase I Inhibition Radiosensitizing Hepatocellular Carcinoma by RNF144A-mediated DNA-PKcs Ubiquitination and Natural Killer Cell Cytotoxicity.Journal of clinical and translational hepatology · 2023Article
- Therapeutic and Diagnostic Potential of Exosomes as Drug Delivery Systems in Brain Cancer.Pharmaceutics · 2023Review
- Targeting DNA-PK.Cancer treatment and research · 2023Article
- The DNA Double-Strand Break Repair in Glioma: Molecular Players and Therapeutic Strategies.Molecular neurobiology · 2022Review
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer.International journal of molecular sciences · 2021Review
- DNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing.Trends in genetics : TIG · 2021Review
- Proteome of Glioblastoma-Derived Exosomes as a Source of Biomarkers.Biomedicines · 2020Article
- DNA-dependent protein kinase promotes DNA end processing by MRN and CtIP.Science advances · 2020Article
- Ring finger protein 121 is a potent regulator of adeno-associated viral genome transcription.PLoS pathogens · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA-dependent protein kinase (DNA-PK) has an important role in the repair of DNA damage and regulates the radiation sensitivity of glioblastoma cells. The VCP (valosine-containing protein), a chaperone protein that regulates ubiquitin-dependent protein degradation, is phosphorylated by DNA-PK and recruited to DNA double-strand break sites to regulate DNA damage repair. However, it is not clear whether VCP is involved in DNA-PKcs (DNA-PK catalytic subunit) degradation or whether it regulates the radiosensitivity of glioblastoma. Our data demonstrated that DNA-PKcs was ubiquitinated and bound to VCP. VCP knockdown resulted in the accumulation of the DNA-PKcs protein in glioblastoma cells, and the proteasome inhibitor MG132 synergised this increase. As expected, this increase promoted the efficiency of DNA repair in several glioblastoma cell lines; in turn, this enhanced activity decreased the radiation sensitivity and prolonged the survival fraction of glioblastoma cells in vitro. Moreover, the VCP knockdown in glioblastoma cells reduced the survival time of the xenografted mice with radiation treatment relative to the control xenografted glioblastoma mice. In addition, the VCP protein was also downregulated in ~25% of GBM tissues from patients (WHO, grade IV astrocytoma), and the VCP protein level was correlated with patient survival (R(2)=0.5222, P<0.05). These findings demonstrated that VCP regulates DNA-PKcs degradation and increases the sensitivity of GBM cells to radiation.
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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.