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Conjugation of complex polyubiquitin chains to WRNIP1.

Werner helicase interacting protein 1 (WRNIP1) is a ubiquitin-binding protein that undergoes extensive post-translational modification including ubiquitination, sumoylation, and phosphorylation. These post-translational modifications are expected to regulate the function of WRNIP1 in the DNA damage response. In this study, we use a denaturing tandem affinity purification technique along with mass spectrometry to show that, unlike most ubiquitin-binding proteins, WRNIP1 is polyubiquitinated. WRNIP1 polyubiquitination is reminiscent of the well-characterized phenomenon of the coupled monoubiquitination of ubiquitin-binding proteins in that this polyubiquitination is dependent on the presence of an intact ubiquitin-binding domain. The polyubiquitin chains conjugated to WRNIP1 are linked through lysines 11, 48, and 63. This study presents the first evidence for the conjugation of K11-K48-K63 polyubiquitin chains to a specific substrate in vivo. Polyubiquitination is likely to regulate WRNIP1's function in the DNA damage response, as UV radiation induces the hyperubiquitination of WRNIP1. Polyubiquitination with noncanonical intraubiquitin linkages may represent a unique mode of regulation of UBZ domain-containing proteins.

Pubmed ID: 18613717


  • Bish RA
  • Fregoso OI
  • Piccini A
  • Myers MP


Journal of proteome research

Publication Data

August 4, 2008

Associated Grants

  • Agency: PHS HHS, Id: 25102067
  • Agency: PHS HHS, Id: 25603521
  • Agency: NIGMS NIH HHS, Id: GM 065094

Mesh Terms

  • Animals
  • Carrier Proteins
  • Cell Line
  • Chromatography, Liquid
  • DNA Damage
  • DNA-Binding Proteins
  • Humans
  • Mice
  • Polyubiquitin
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Ubiquitination
  • Ultraviolet Rays