ArticleProceedings of the National Academy of Sciences of the United States of America2002
Apoptotic threshold is lowered by p53 transactivation of caspase-6.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 162 citations in OpenAlex.
- Points of Departure for BPDE-induced cellular senescence and cell death are characterized by altered DNA damage signaling and regulated by unrepaired DNA double-strand breaks.Archives of toxicology · 2026Article
- APP-C31 pathology as a target in neurodegenerative diseases.Journal of biomedical science · 2026Review
- Interpretable identification of cancer genes across biological networks via transformer-powered graph representation learning.Nature biomedical engineering · 2025Article
- Static Magnetic Stimulation and Magnetic Microwires Synergistically Enhance and Guide Neurite Outgrowth.Advanced healthcare materials · 2025Article
- Strong activation of p53 by actinomycin D and nutlin-3a overcomes the resistance of cancer cells to the pro-apoptotic activity of the FAS ligand.Apoptosis : an international journal on programmed cell death · 2024Article
- Design and mathematical analysis of activating transcriptional amplifiers that enable modular temporal control in synthetic juxtacrine circuits.Synthetic and systems biotechnology · 2023Article
- A Review on Caspases: Key Regulators of Biological Activities and Apoptosis.Molecular neurobiology · 2023Review
- Interlukin-4 weakens resistance to stress injury and megakaryocytic differentiation of hematopoietic stem cells by inhibiting Psmd13 expression.Scientific reports · 2023Article
- Selective chemical reagents to investigate the role of caspase 6 in apoptosis in acute leukemia T cells.Chemical science · 2023Article
- Crosstalk of the Wnt/β-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Role of ARK5 in cancer and other diseases (Review).Experimental and therapeutic medicine · 2021Review
- Rare CASP6N73T variant associated with hippocampal volume exhibits decreased proteolytic activity, synaptic transmission defect, and neurodegeneration.Scientific reports · 2021Article
- Cytoplasmic Mixing, Not Nuclear Coexistence, Can Explain Somatic Incompatibility in Basidiomycetes.Microorganisms · 2021Review
- Role of Dietary Antioxidants in p53-Mediated Cancer Chemoprevention and Tumor Suppression.Oxidative medicine and cellular longevity · 2021Review
- Caspase-6 Knockout in the 5xFAD Model of Alzheimer's Disease Reveals Favorable Outcome on Memory and Neurological Hallmarks.International journal of molecular sciences · 2020Article
- Neonatal Alcohol Exposure in Mice Induces Select Differentiation- and Apoptosis-Related Chromatin Changes Both Independent of and Dependent on Sex.Frontiers in genetics · 2020Article
- Site-specific phosphorylation and caspase cleavage of GFAP are new markers of Alexander disease severity.eLife · 2019Article
- Mechanism of Apoptosis Induced by Curcumin in Colorectal Cancer.International journal of molecular sciences · 2019Review
- Reciprocal negative regulation between the tumor suppressor protein p53 and B cell CLL/lymphoma 6 (BCL6) via control of caspase-1 expression.The Journal of biological chemistry · 2019Article
- A2B adenosine receptor agonist induces cell cycle arrest and apoptosis in breast cancer stem cells via ERK1/2 phosphorylation.Cellular oncology (Dordrecht, Netherlands) · 2018Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Little is known about how a cell's apoptotic threshold is controlled after exposure to chemotherapy, although the p53 tumor suppressor has been implicated. We identified executioner caspase-6 as a transcriptional target of p53. The mechanism involves DNA binding by p53 to the third intron of the caspase-6 gene and transactivation. A p53-dependent increase in procaspase-6 protein level allows for an increase in caspase-6 activity and caspase-6-specific Lamin A cleavage in response to Adriamycin exposure. Specific inhibition of caspase-6 blocks cell death in a manner that correlates with caspase-6 mRNA induction by p53 and enhances long-term survival in response to a p53-mediated apoptotic signal. Caspase-6 is an executioner caspase found directly regulated by p53, and the most downstream component of the death pathway controlled by p53. The induction of caspase-6 expression lowers the cell death threshold in response to apoptotic signals that activate caspase-6. Our results provide a potential mechanism of lowering the death threshold, which could be important for chemosensitization.
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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.