The proteasome is an integral part of solar ultraviolet a radiation-induced gene expression

J Biol Chem. 2009 Oct 30;284(44):30076-86. doi: 10.1074/jbc.M109.044503. Epub 2009 Aug 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Fibroblasts / radiation effects
  • Gene Expression Regulation / radiation effects*
  • Humans
  • Matrix Metalloproteinase 1 / genetics
  • Proteasome Endopeptidase Complex / genetics*
  • Signal Transduction
  • Skin / cytology
  • Skin / radiation effects
  • Stress, Physiological
  • Sunlight
  • Ultraviolet Rays*


  • Matrix Metalloproteinase 1
  • Proteasome Endopeptidase Complex