title: The proteasome is an integral part of solar ultraviolet a radiation-induced gene expression.
abstract: 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.
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, 70593 Stuttgart, Germany.
authors.forename: Betul
authors.initials: B
authors.lastname: Catalgol
authors.forename: Isabella
authors.initials: I
authors.lastname: Ziaja
authors.forename: Nicolle
authors.initials: N
authors.lastname: Breusing
authors.forename: Tobias
authors.initials: T
authors.lastname: Jung
authors.forename: Annika
authors.initials: A
authors.lastname: Höhn
authors.forename: Buket
authors.initials: B
authors.lastname: Alpertunga
authors.forename: Peter
authors.initials: P
authors.lastname: Schroeder
authors.forename: Niki
authors.initials: N
authors.lastname: Chondrogianni
authors.forename: Efstathios S
authors.initials: ES
authors.lastname: Gonos
authors.forename: Isabelle
authors.initials: I
authors.lastname: Petropoulos
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
authors.forename: Lars-Oliver
authors.initials: LO
authors.lastname: Klotz
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
mesh_terms: 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
chemical_list: D020781:Matrix Metalloproteinase 1; D046988:Proteasome Endopeptidase Complex
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