Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation

Ellen Fritsche, Claudia Schäfer, Christian Calles, Thorsten Bernsmann, Thorsten Bernshausen, Melanie Wurm, Ulrike Hübenthal, Jason E. Cline, Hossein Hajimiragha, Peter Schroeder, Lars Oliver Klotz, Agneta Rannug, Peter Fürst, Helmut Hanenberg, Josef Abel, Jean Krutmann

Research output: Contribution to journalArticlepeer-review

290 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8851-8856
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number21
DOIs
StatePublished - May 22 2007

Keywords

  • 6-formylindolo[3,2-b]carbazole
  • Cyclooxygenase-2
  • EGF receptor
  • Src
  • UVB

ASJC Scopus subject areas

  • General

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