ArticleThe Journal of biological chemistry2013
The Arf/p53 protein module, which induces apoptosis, down-regulates histone H2AX to allow normal cells to survive in the presence of anti-cancer drugs.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Genome destabilization-associated phenotypes arising as a consequence of therapeutic treatment are suppressed by Olaparib.PloS one · 2023Article
- Genomic Instability and Cancer Risk Associated with Erroneous DNA Repair.International journal of molecular sciences · 2021Review
- Genomic destabilization and its associated mutagenesis increase with senescence-associated phenotype expression.Cancer science · 2021Review
- New Oleoyl Hybrids of Natural Antioxidants: Synthesis and In Vitro Evaluation as Inducers of Apoptosis in Colorectal Cancer Cells.Antioxidants (Basel, Switzerland) · 2020Article
- Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability.Scientific reports · 2020Article
- Mismatch repair dependence of replication stress-associated DSB recognition and repair.Heliyon · 2019Article
- Genomic-Destabilization-Associated Mutagenesis and Clonal Evolution of Cells with Mutations in Tumor-Suppressor Genes.Cancers · 2019Review
- Replication stress triggers microsatellite destabilization and hypermutation leading to clonal expansion in vitro.Nature communications · 2019Article
- Stemness, Pluripotentiality, and Wnt Antagonism: sFRP4, a Wnt antagonist Mediates Pluripotency and Stemness in Glioblastoma.Cancers · 2018Article
- Review
- Neurotoxicity of cytarabine (Ara-C) in dorsal root ganglion neurons originates from impediment of mtDNA synthesis and compromise of mitochondrial function.Free radical biology & medicine · 2018Article
- Comparative Transcriptomics Unravels Prodigiosin's Potential Cancer-Specific Activity Between Human Small Airway Epithelial Cells and Lung Adenocarcinoma Cells.Frontiers in oncology · 2018Article
- Cisplatin Toxicity in Dorsal Root Ganglion Neurons Is Relieved by Meclizine via Diminution of Mitochondrial Compromise and Improved Clearance of DNA Damage.Molecular neurobiology · 2017Article
- Article
- Article
- Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM/ATR signaling.Oncotarget · 2016Article
- A comprehensive analysis of radiosensitization targets; functional inhibition of DNA methyltransferase 3B radiosensitizes by disrupting DNA damage regulation.Scientific reports · 2015Article
- Development of cancer-initiating cells and immortalized cells with genomic instability.World journal of stem cells · 2015Review
- Citrate synthase expression affects tumor phenotype and drug resistance in human ovarian carcinoma.PloS one · 2014Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIt is unclear how DNA-damaging agents target cancer cells over normal somatic cells.
resultsArf/p53-dependent down-regulation of H2AX enables normal cells to survive after DNA damage.
conclusionTransformed cells, which harbor mutations in either Arf or p53, are more sensitive to DNA-damaging agents. SIGNIFICANCE: Cellular transformation renders cells more susceptible to some DNA-damaging agents. Anti-cancer drugs generally target cancer cells rather than normal somatic cells. However, the factors that determine this differential sensitivity are poorly understood. Here we show that Arf/p53-dependent down-regulation of H2AX induced the selective survival of normal cells after drug treatment, resulting in the preferential targeting of cancer cells. Treatment with camptothecin, a topoisomerase I inhibitor, caused normal cells to down-regulate H2AX and become quiescent, a process mediated by both Arf and p53. In contrast, transformed cells that harbor mutations in either Arf or p53 do not down-regulate H2AX and are more sensitive to drugs unless they have developed drug resistance. Such transformation-associated changes in H2AX expression rendered cancer cells more susceptible to drug-induced damage (by two orders of magnitude). Thus, the expression of H2AX and γH2AX (phosphorylated form of H2AX at Ser-139) is a critical factor that determines drug sensitivity and should be considered when administering chemotherapy.
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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.