The proteasome is an integral part of solar ultraviolet a radiation-induced gene expression.
Solar ultraviolet (UV) A radiation is a well known trigger of signaling responses in human skin fibroblasts. One important consequence of this stress response is the increased expression of matrix metalloproteinase-1 (MMP-1), which causes extracellular protein degradation and thereby contributes to photoaging of human skin. In the present study we identify the proteasome as an integral part of the UVA-induced, intracellular signaling cascade in human dermal fibroblasts. UVA-induced singlet oxygen formation was accompanied by protein oxidation, the cross-linking of oxidized proteins, and an inhibition of the proteasomal system. This proteasomal inhibition subsequently led to an accumulation of c-Jun and phosphorylated c-Jun and activation of activator protein-1, i.e. transcription factors known to control MMP-1 expression. Increased transcription factor activation was also observed if the proteasome was inhibited by cross-linked proteins or lactacystin, indicating a general mechanism. Most importantly, inhibition of the proteasome was of functional relevance for UVA-induced MMP-1 expression, because overexpression of the proteasome or the protein repair enzyme methionine sulfoxide reductase prevented the UVA-induced induction of MMP-1. These studies show that an environmentally relevant stimulus can trigger a signaling pathway, which links intracellular and extracellular protein degradation. They also identify the proteasome as an integral part of the UVA stress response.
Catalgol
Betul
B
Institute of Biological Chemistry and Nutrition, University of Hohenheim, 70593 Stuttgart, Germany.
Ziaja
Isabella
I
Breusing
Nicolle
N
Jung
Tobias
T
Höhn
Annika
A
Alpertunga
Buket
B
Schroeder
Peter
P
Chondrogianni
Niki
N
Gonos
Efstathios S
ES
Petropoulos
Isabelle
I
Friguet
Bertrand
B
Klotz
Lars-Oliver
LO
Krutmann
Jean
J
Grune
Tilman
T
D002478:Cells, Cultured; D005347:Fibroblasts / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000528:radiation effects; D013312:Stress, Physiological; D013472:Sunlight; D014466:Ultraviolet Rays
D020781:Matrix Metalloproteinase 1; D046988:Proteasome Endopeptidase Complex
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