Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation
Open accessAbstract
UVB radiation-induced signaling in mammalian cells involves two major pathways: one that is initiated through the generation of DNA photoproducts in the nucleus and a second one that occurs independently of DNA damage and is characterized by cell surface receptor activation. The chromophore for the latter one has been unknown. Here, we report that the UVB response involves tryptophan as a chromophore. We show that through the intracellular generation of photoproducts, such as the arylhydrocarbon receptor (AhR) ligand 6-formylindolo[3,2- b ]carbazole, signaling events are initiated, which are transferred to the nucleus and the cell membrane via activation of the cytoplasmatic AhR. Specifically, AhR activation by UVB leads to ( i ) transcriptional induction of cytochrome P450 1A1 and ( ii ) EGF receptor internalization with activation of the EGF receptor downstream target ERK1/2 and subsequent induction of cyclooxygenase-2. The role of the AhR in the UVB stress response was confirmed in vivo by studies employing AhR KO mice.
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PAHs are potent activators of AhR, which is expressed in keratinocytes and melanocytes.
“PAHs are potent activators of the aryl hydrocarbon receptor (AhR), which is a ligand-dependent transcription factor expressed in keratinocytes and melanocytes (Fritsche et al. 2007; Jux et al. 2011).”
From Particulate matter 2.5 damages skin cells by inducing oxidative stress, subcellular organelle dysfunction, and apoptosis (2018) · cites this paper as Fritsche et al. 2007
The introductory passage (page unavailable) describes AhR as a ligand-dependent receptor that mediates PAH toxicity and activates gene transcription after ligand binding. The Results and Discussion show AhR signaling in HaCaT keratinocytes, but the copy does not establish AhR expression in melanocytes or specifically describe PAHs as potent activators. (LLM, conf=0.86)
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- Authors
- Fritsche, E., Schäfer, C., Calles, C., Bernsmann, T., Bernshausen, T., Wurm, M., Hübenthal, U., Cline, J. E., Hajimiragha, H., Schroeder, P., Klotz, L.-O., Rannug, A., Fürst, P., Hanenberg, H., Abel, J., & Krutmann, J.
- Affiliations
- Leibniz Institute of Environmental Medicine (DE)
- Chemical and Veterinary Control Laboratory, Josef-König-Strasse 40, 48147 Münster, Germany;
- Heinrich Heine University Düsseldorf (DE)
- *Institut für Umweltmedizinische Forschung (IUF), Auf'm Hennekamp 50, 40225 Düsseldorf, Germany;
- Karolinska Institutet (SE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-05-22
- Volume
- 104
- Issue
- 21
- Pages
- 8851-8856
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1885591
- OpenAlex
- W2071813734
- Cited by
- 437
- References
- 50
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 18 · 2023: 16 · 2022: 22 · 2021: 24 · 2020: 19 · 2019: 23 · 2018: 35 · 2017: 24 · 2016: 21 · 2015: 25 · 2014: 25 · 2013: 19 · 2012: 29
- FWCI
- 22.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- UV-B radiation, aryl hydrocarbon receptor, FICZ, DNA photoproducts, CYP1A1, ERK signaling, cyclooxygenase-2, AhR knockout mice
- MeSH terms
- Animals, Carbazoles, Cell Line, Cell Nucleus, Cytoplasm, Gene Expression Regulation, Humans, Indoles, Transcription, Genetic, Tryptophan, Ultraviolet Rays, Molecular Structure, Signal Transduction, Proto-Oncogene Proteins pp60(c-src), Receptors, Aryl Hydrocarbon, Mice, Knockout, Cytochrome P-450 CYP1A1, Active Transport, Cell Nucleus, Mice, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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