Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation.
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.
Fritsche
Ellen
E
Institut für Umweltmedizinische Forschung (IUF), Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
Schäfer
Claudia
C
Calles
Christian
C
Bernsmann
Thorsten
T
Bernshausen
Thorsten
T
Wurm
Melanie
M
Hübenthal
Ulrike
U
Cline
Jason E
JE
Hajimiragha
Hossein
H
Schroeder
Peter
P
Klotz
Lars-Oliver
LO
Rannug
Agneta
A
Fürst
Peter
P
Hanenberg
Helmut
H
Abel
Josef
J
Krutmann
Jean
J
D021581:Active Transport, Cell Nucleus; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002227:Carbazoles / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism* / Q000528:radiation effects*; D066246:ErbB Receptors / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects; D014158:Transcription, Genetic / Q000235:genetics; D014364:Tryptophan / Q000378:metabolism; D014466:Ultraviolet Rays
D051792:Basic Helix-Loop-Helix Proteins; D002227:Carbazoles; D019363:Cytochrome P-450 CYP1A1; D066246:ErbB Receptors; D007211:Indoles; D016392:Proto-Oncogene Proteins pp60(c-src); D018336:Receptors, Aryl Hydrocarbon; D014364:Tryptophan; C111855:6-formylindolo(3,2-b)carbazole; C111235:AHR protein, human; C484722:Ahr protein, mouse