The Proteasome Is an Integral Part of Solar Ultraviolet A Radiation-induced Gene Expression

• Published in: The Journal of biological chemistry Vol. 284; no. 44; pp. 30076 - 30086
• Main Authors: Catalgol, Betul, Ziaja, Isabella, Breusing, Nicolle, Jung, Tobias, Höhn, Annika, Alpertunga, Buket, Schroeder, Peter, Chondrogianni, Niki, Gonos, Efstathios S., Petropoulos, Isabelle, Friguet, Bertrand, Klotz, Lars-Oliver, Krutmann, Jean, Grune, Tilman
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30-10-2009; American Society for Biochemistry and Molecular Biology
• Subjects: Cells, Cultured; Fibroblasts - radiation effects; Gene Expression Regulation - radiation effects; Humans; Matrix Metalloproteinase 1 - genetics; Mechanisms of Signal Transduction; Proteasome Endopeptidase Complex - genetics; Signal Transduction; Skin - cytology; Skin - radiation effects; Stress, Physiological; Sunlight; Ultraviolet Rays
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.044503

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.