ArticleCell death and differentiation2013
Evidence for a novel anti-apoptotic pathway in human keratinocytes involving the aryl hydrocarbon receptor, E2F1, and checkpoint kinase 1.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Benzo[a]pyrene vs. Tapinarof: unraveling ligand-specific AHR transcriptional responses in immortalized keratinocytes.Archives of toxicology · 2026Article
- Aryl hydrocarbon receptor is involved in DNA damage repair after liver injury with diethylnitrosamine in mice.Molecular biomedicine · 2026Article
- Melatonin Regulates Arylhydrocarbon Receptor Mediated UVR-Induced Processes Related to Inflammation, Skin Aging and Carcinogenesis in Human Ex Vivo Skin.Experimental dermatology · 2026Article
- Targeting aryl hydrocarbon receptor to prevent cancer in barrier organs.Biochemical pharmacology · 2024Review
- Aryl hydrocarbon receptor role in chronic inflammatory skin diseases: a narrative review.Postepy dermatologii i alergologii · 2024Review
- The Aryl Hydrocarbon Receptor: Impact on the Tumor Immune Microenvironment and Modulation as a Potential Therapy.Cancers · 2024Review
- Aryl hydrocarbon receptor is a tumor promoter iniScience · 2023Article
- 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
- Aryl Hydrocarbon Receptor Promotes Cell Growth, Stemness Like Characteristics, and Metastasis in Human Ovarian Cancer via Activation of PI3K/Akt, β-Catenin, and Epithelial to Mesenchymal Transition Pathways.International journal of molecular sciences · 2022Article
- UVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR- and SP1-dependent manner.JCI insight · 2022Article
- The Aryl Hydrocarbon Receptor in the Pathogenesis of Environmentally-Induced Squamous Cell Carcinomas of the Skin.Frontiers in oncology · 2022Review
- Review
- 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
- How the AHR Became Important in Cancer: The Role of Chronically Active AHR in Cancer Aggression.International journal of molecular sciences · 2020Review
- Article
- The UVR Filter Octinoxate Modulates Aryl Hydrocarbon Receptor Signaling in Keratinocytes via Inhibition of CYP1A1 and CYP1B1.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Role of the Aryl Hydrocarbon Receptor in Environmentally Induced Skin Aging and Skin Carcinogenesis.International journal of molecular sciences · 2019Review
- Aryl Hydrocarbon Receptor Modulates Carcinogenesis and Maintenance of Skin Cancers.Frontiers in medicine · 2019Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure of keratinocytes (KC) to ultraviolet (UV) radiation results in the initiation of apoptosis, a protective mechanism that eliminates cells harboring irreparable DNA damage. Hence, a manipulation of UV-induced apoptosis may significantly influence photocarcinogenesis. We have discovered that the aryl hydrocarbon receptor (AHR), a key regulator of drug metabolism and an UVB-sensitive transcription factor, serves an anti-apoptotic function in UVB-irradiated human KC. Chemical and shRNA-mediated inhibition of AHR signaling sensitized KC to UVB-induced apoptosis by decreasing the expression of E2F1 and its target gene checkpoint kinase 1 (CHK1). The decreased expression of these cell-cycle regulators was due to an enhanced expression of p27(KIP1) and an associated decrease in phosphorylation of both cyclin-dependent kinase 2 and its substrate molecule retinoblastoma protein. The subsequent inhibition of E2F1 autoregulation and downstream CHK1 expression resulted in an enhanced susceptibility of damaged cells to undergo apoptosis. Accordingly, ectopic overexpression of either E2F1 or CHK1 in AHR-knockdown KC attenuated the observed sensitization to UVB-induced apoptosis. Using an AHR-knockout SKH-1 hairless mouse model, we next demonstrated the physiological relevance of the anti-apoptotic function of AHR. In contrast to their AHR-proficient littermates, the constitutive expression of E2F1 and CHK1 was significantly reduced in the skin of AHR-knockout mice. Accordingly, a single exposure of the animals to UVB resulted in an enhanced cleavage of caspase-3 in the skin of AHR-knockout mice. These results identify for the first time the AHR-E2F1-CHK1 axis as a novel anti-apoptotic pathway in KC, which may represent a suitable target for chemoprevention of non-melanoma skin cancer.
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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.