An N-terminal SIAH-interacting motif regulates the stability of the ubiquitin specific protease (USP)-19

Biochem Biophys Res Commun. 2013 Apr 19;433(4):390-5. doi: 10.1016/j.bbrc.2013.02.094. Epub 2013 Mar 13.

Abstract

The Ubiquitin Specific Protease-19 (USP19) regulates cell cycle progression and is involved in the cellular response to different types of stress, including the unfolded protein response (UPR), hypoxia and muscle atrophy. Using the unique N-terminal domain as bait in a yeast-two hybrid screen we have identified the ubiquitin ligases Seven In Absentia Homolog (SIAH)-1 and SIAH2 as binding partners of USP19. The interaction is mediated by a SIAH-consensus binding motif and promotes USP19 ubiquitylation and proteasome-dependent degradation. These findings identify USP19 as a common substrate of the SIAH ubiquitin ligases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Blotting, Western
  • Computational Biology / methods
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • Enzyme Stability
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Binding
  • Protein Interaction Mapping
  • Proteolysis
  • Two-Hybrid System Techniques
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination

Substances

  • Nuclear Proteins
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins
  • Endopeptidases
  • USP19 protein, human
  • Proteasome Endopeptidase Complex