Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation
Autor: | Ulrike Hübenthal, Peter Fürst, Jason E. Cline, Ellen Fritsche, Helmut Hanenberg, Hossein Hajimiragha, Thorsten Bernsmann, Claudia Schäfer, Peter Schroeder, Jean Krutmann, Lars-Oliver Klotz, Josef Abel, Melanie Wurm, Christian Calles, Thorsten Bernshausen, Agneta Rannug |
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Jazyk: | angličtina |
Rok vydání: | 2007 |
Předmět: |
Cytoplasm
Indoles Transcription Genetic DNA damage Ultraviolet Rays Proto-Oncogene Proteins pp60(c-src) Active Transport Cell Nucleus Carbazoles Biology Cell Line Cell membrane Mice Cell surface receptor medicine Basic Helix-Loop-Helix Transcription Factors Cytochrome P-450 CYP1A1 Animals Humans Receptor Cell Nucleus Mice Knockout Multidisciplinary Molecular Structure Tryptophan Biological Sciences Ligand (biochemistry) Molecular biology ErbB Receptors medicine.anatomical_structure Gene Expression Regulation Receptors Aryl Hydrocarbon Signal transduction Intracellular Signal Transduction |
Popis: | 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. |
Databáze: | OpenAIRE |
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