ArticleMolecular and cellular biology2009
Death receptor-induced activation of the Chk2- and histone H2AX-associated DNA damage response pathways.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 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.
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Who cites it
65 citing papers in PubMed, 106 citations in OpenAlex.
- Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer.PloS one · 2015Trial
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- 1,2-Dichloropropane, but not dichloromethane or trichloropropane, reduces apoptosis of human cholangiocytes co-cultured with macrophages.Journal of occupational health · 2026Article
- Histone Phosphorylation in DNA Damage Response.International journal of molecular sciences · 2025Review
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- Immunohistochemical Pattern of Histone H2A Variant Expression in an Experimental Model of Ischemia-Reperfusion-Induced Acute Kidney Injury.International journal of molecular sciences · 2023Article
- Maternal Serum tRNA-Derived Fragments (tRFs) as Potential Candidates for Diagnosis of Fetal Congenital Heart Disease.Journal of cardiovascular development and disease · 2023Article
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- Porcine Enteric Coronavirus PEDV Induces the ROS-ATM and Caspase7-CAD-γH2AX Signaling Pathways to Foster Its Replication.Viruses · 2022Article
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- The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age.Molecules (Basel, Switzerland) · 2021Review
- Mutagenic Consequences of Sublethal Cell Death Signaling.International journal of molecular sciences · 2021Review
- dSTORM microscopy evidences in HeLa cells clustered and scattered γH2AX nanofoci sensitive to ATM, DNA-PK, and ATR kinase inhibitors.Molecular and cellular biochemistry · 2020Article
- Schistosoma mansoni Egg-Secreted Antigens Activate Hepatocellular Carcinoma-Associated Transcription Factors c-Jun and STAT3 in Hamster and Human Hepatocytes.Hepatology (Baltimore, Md.) · 2020Article
- Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells.Scientific reports · 2019Article
- Typhoid toxin exhausts the RPA response to DNA replication stress driving senescence and Salmonella infection.Nature communications · 2019Article
- Polynuclear ruthenium organometallic compounds induce DNA damage in human cells identified by the nucleotide excision repair factor XPC.Bioscience reports · 2019Article
- Escherichia Coli Outer Membrane Vesicles Induced DNA Double-Strand Breaks in Intestinal Epithelial Caco-2 Cells.Medical science monitor basic research · 2019Article
- Checkpoint kinase inhibitor AZD7762 enhance cisplatin-induced apoptosis in osteosarcoma cells.Cancer cell international · 2019Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
TRAIL is an endogenous death receptor ligand also used therapeutically because of its selective proapoptotic activity in cancer cells. In the present study, we examined chromatin alterations induced by TRAIL and show that TRAIL induces a rapid activation of DNA damage response (DDR) pathways with histone H2AX, Chk2, ATM, and DNA-PK phosphorylations. Within 1 h of TRAIL exposure, immunofluorescence confocal microscopy revealed gamma-H2AX peripheral nuclear staining (gamma-H2AX ring) colocalizing with phosphorylated/activated Chk2, ATM, and DNA-PK inside heterochromatin regions. The marginal distribution of DDR proteins in early apoptotic cells is remarkably different from the focal staining seen after DNA damage. TRAIL-induced DDR was suppressed upon caspase inhibition or Bax inactivation, demonstrating that the DDR activated by TRAIL is downstream from the mitochondrial death pathway. H2AX phosphorylation was dependent on DNA-PK, while Chk2 phosphorylation was dependent on both ATM and DNA-PK. Downregulation of Chk2 decreased TRAIL-induced cell detachment; delayed the activation of caspases 2, 3, 8, and 9; and reduced TRAIL-induced cell killing. Together, our findings suggest that nuclear activation of Chk2 by TRAIL acts as a positive feedback loop involving the mitochondrion-dependent activation of caspases, independently of p53.
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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.