ArticleProceedings of the National Academy of Sciences of the United States of America2009
EGF receptor signaling blocks aryl hydrocarbon receptor-mediated transcription and cell differentiation in human epidermal keratinocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 98 citations in OpenAlex.
- Comparative 28-day mouse study of topically applied aryl hydrocarbon receptor ligands: microbiota-derived indoles, therapeutic tapinarof, pollutants 2,3,7,8-tetrachlorodibenzo-p-dioxin and diesel exhaust particles.Chemico-biological interactions · 2026Article
- The aryl hydrocarbon receptor: structure, signaling, physiology and pathology.Signal transduction and targeted therapy · 2026Review
- The Aryl Hydrocarbon Receptor (AHR): Peacekeeper of the Skin.International journal of molecular sciences · 2025Review
- Polybrominated diphenyl ether flame retardants inhibit growth factor-induced activation of EGFR by binding to its extracellular domain.Archives of toxicology · 2025Article
- Ligand Activation of the Aryl Hydrocarbon Receptor Upregulates Epidermal Uridine Diphosphate Glucose Ceramide Glucosyltransferase and Glucosylceramides.The Journal of investigative dermatology · 2023Article
- Environmental Air Pollutants Affecting Skin Functions with Systemic Implications.International journal of molecular sciences · 2023Review
- Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway.Biochemical pharmacology · 2023Review
- Management of Plaque Psoriasis in Adults: Clinical Utility of Tapinarof Cream.Psoriasis (Auckland, N.Z.) · 2023Review
- CYP1B1 Augments the Mesenchymal, Claudin-Low, and Chemoresistant Phenotypes of Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Manipulating Microbiota to Treat Atopic Dermatitis: Functions and Therapies.Pathogens (Basel, Switzerland) · 2022Review
- Unraveling the differential impact of PAHs and dioxin-like compounds on AKR1C3 reveals the EGFR extracellular domain as a critical determinant of the AHR response.Environment international · 2022Article
- Review
- Cutaneous Effects of In Utero and Lactational Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-Toxics · 2021Article
- Commensal microbiota regulates skin barrier function and repair via signaling through the aryl hydrocarbon receptor.Cell host & microbe · 2021Article
- Ultraviolet Radiation and Chronic Inflammation-Molecules and Mechanisms Involved in Skin Carcinogenesis: A Narrative Review.Life (Basel, Switzerland) · 2021Review
- Trajectory Shifts in Interdisciplinary Research of the Aryl Hydrocarbon Receptor-A Personal Perspective on Thymus and Skin.International journal of molecular sciences · 2021Review
- A New Insight into the Potential Role of Tryptophan-Derived AhR Ligands in Skin Physiological and Pathological Processes.International journal of molecular sciences · 2021Review
- IL-24 Negatively Regulates Keratinocyte Differentiation Induced by Tapinarof, an Aryl Hydrocarbon Receptor Modulator: Implication in the Treatment of Atopic Dermatitis.International journal of molecular sciences · 2020Article
- Contributions of Nitric Oxide to AHR-Ligand-Mediated Keratinocyte Differentiation.International journal of molecular sciences · 2020Article
- Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis.International journal of molecular sciences · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Dioxin is an extremely potent carcinogen. In highly exposed people, the most commonly observed toxicity is chloracne, a pathological response of the skin. Most of the effects of dioxin are attributed to its activation of the aryl hydrocarbon receptor (AHR), a transcription factor that binds to the Ah receptor nuclear translocator (ARNT) to regulate the transcription of numerous genes, including CYP1A1 and CYP1B1. In cultures of normal human epidermal keratinocytes dioxin accelerates cell differentiation, as measured by the formation of cornified envelopes. We show that this acceleration is mediated by the AHR; also, that dioxin increases the expression of several genes known to be regulated by ARNT, which have critical roles in the cornification and epidermal barrier function of the skin. Importantly, we demonstrate that all of these responses are opposed by ligand-activation of the EGF receptor (R), an important regulator of keratinocyte cell fate. In the CYP1A1 enhancer, EGFR activation prevents recruitment of the p300 coactivator, although not affecting the binding of the AHR or ARNT. The total cellular level of p300 protein does not decrease, and overexpression of p300 relieves EGFR-mediated repression of transcription, indicating that p300 is a critical target for the repression of the AHR complex by EGFR signaling. These results provide a mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin is able to disrupt epidermal homeostasis and identify EGFR signaling as a regulator of the AHR. This signaling may modulate the incidence and severity of chloracne and be of therapeutic relevance to human poisonings by dioxin.
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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.