ArticleJournal of immunology (Baltimore, Md. : 1950)2007
A novel mode of action for a microbial-derived immunotoxin: the cytolethal distending toxin subunit B exhibits phosphatidylinositol 3,4,5-triphosphate phosphatase activity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 113 citations in OpenAlex.
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- TM9SF4 acts as a receptor mediatingFrontiers in cellular and infection microbiology · 2026Article
- Bacterial small molecule metabolites implicated in gastrointestinal cancer development.Nature reviews. Microbiology · 2025Review
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- Cellugyrin (synaptogyrin-2) dependent pathways are used by bacterial cytolethal distending toxin and SARS-CoV-2 virus to gain cell entry.Frontiers in cellular and infection microbiology · 2024Article
- Delivery, structure, and function of bacterial genotoxins.Virulence · 2022Review
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- Advances in the Study of Bacterial Toxins, Their Roles and Mechanisms in Pathogenesis.The Malaysian journal of medical sciences : MJMS · 2022Review
- Review
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- Cytolethal distending toxin: from genotoxin to a potential biomarker and anti-tumor target.World journal of microbiology & biotechnology · 2021Review
- The Active Subunit of the Cytolethal Distending Toxin, CdtB, Derived From BothFrontiers in cellular and infection microbiology · 2021Article
- Functional Study ofToxins · 2020Article
- Cytolethal distending toxin-induced release of interleukin-1β by human macrophages is dependent upon activation of glycogen synthase kinase 3β, spleen tyrosine kinase (Syk) and the noncanonical inflammasome.Cellular microbiology · 2020Article
- Bacterial Genotoxin-Induced DNA Damage and Modulation of the Host Immune Microenvironment.Toxins · 2020Review
- The Cell-Cycle Regulatory Protein p21Pathogens (Basel, Switzerland) · 2020Article
- Oral and intestinal bacterial exotoxins: Potential linked to carcinogenesis.Progress in molecular biology and translational science · 2020Review
- Review
- Genome-Wide Identification of Host Genes Required for Toxicity of Bacterial Cytolethal Distending Toxin in a Yeast Model.Frontiers in microbiology · 2019Article
- Mechanisms of Oral Bacterial Virulence Factors in Pancreatic Cancer.Frontiers in cellular and infection microbiology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The Actinobacillus actinomycetemcomitans cytolethal distending toxin (Cdt) is a potent immunotoxin that induces G(2) arrest in human lymphocytes. We now show that the CdtB subunit exhibits phosphatidylinositol (PI)-3,4,5-triphosphate phosphatase activity. Breakdown product analysis indicates that CdtB hydrolyzes PI-3,4,5-P(3) to PI-3,4-P(2) and therefore functions in a manner similar to phosphatidylinositol 5-phosphatases. Conserved amino acids critical to catalysis in this family of enzymes were mutated in the cdtB gene. The mutant proteins exhibit reduced phosphatase activity along with decreased ability to induce G(2) arrest. Consistent with this activity, Cdt induces time-dependent reduction of PI-3,4,5-P(3) in Jurkat cells. Lymphoid cells with defects in SHIP1 and/or ptase and tensin homolog deleted on chromosome 10 (PTEN) (such as Jurkat, CEM, Molt) and, concomitantly, elevated PI-3,4,5-P(3) levels were more sensitive to the toxin than HUT78 cells which contain functional levels of both enzymes and low levels of PI-3,4,5-P(3). Finally, reduction of Jurkat cell PI-3,4,5-P(3) synthesis using the PI3K inhibitors, wortmannin and LY290004, protects cells from toxin-induced cell cycle arrest. Collectively, these studies show that the CdtB not only exhibits PI-3,4,5-P(3) phosphatase activity, but also that toxicity in lymphocytes is related to this activity.
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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.