UV radiation regulates Mi-2 through protein translation and stability

J Biol Chem. 2008 Dec 12;283(50):34976-82. doi: 10.1074/jbc.M805383200. Epub 2008 Oct 15.

Abstract

Dermatomyositis (DM) is an autoimmune disease, which is often accompanied by the development of disease-specific autoantibodies directed against the SNF2-superfamily helicase, Mi-2. Recent evidence suggests that ultraviolet radiation exposure may be an important risk factor for the development of not only the disease but also specific autoimmunity against Mi-2. Consequently, we investigated the effects of ultraviolet radiation on Mi-2 protein expression. We observed an increase in protein levels upon ultraviolet radiation exposure in cell culture systems. These changes in expression occur quite rapidly, are maximized just 1 h following exposure, and are unique to Mi-2 when compared with other members of the NuRD complex. Changes in protein levels are not mediated through transcriptional mechanisms. Treatment results in a more efficiently translated message through regulatory elements in the 5'-UTR region of the transcript. Investigation into protein half-life further demonstrated increased stability of Mi-2 following UV exposure. Taken together, we describe a system by which Mi-2 protein expression can be quickly increased following UV exposure and then maintained up to 16 h later. These data provide a novel regulation of an important transcriptional regulator and provide insight into the possible mechanisms of the development of DM and associated autoantibodies.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • 5' Untranslated Regions
  • Autoantibodies / chemistry
  • Autoantigens / metabolism*
  • Cell Line, Tumor
  • Cell Separation
  • DNA Helicases / metabolism*
  • Flow Cytometry
  • Humans
  • Keratinocytes / metabolism
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Models, Biological
  • Plasmids / metabolism
  • Protein Biosynthesis / radiation effects*
  • Risk Factors
  • Time Factors
  • Transcription, Genetic
  • Ultraviolet Rays*

Substances

  • 5' Untranslated Regions
  • Autoantibodies
  • Autoantigens
  • CHD4 protein, human
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • DNA Helicases