A SIM-ultaneous role for SUMO and ubiquitin

Trends Biochem Sci. 2008 May;33(5):201-8. doi: 10.1016/j.tibs.2008.02.001. Epub 2008 Apr 9.


Ubiquitin and ubiquitin-like proteins (Ubls) share a beta-GRASP fold and have key roles in cellular growth and suppression of genome instability. Despite their common fold, SUMO and ubiquitin are classically portrayed as distinct, and they can have antagonistic roles. Recently, a new family of proteins, the small ubiquitin-related modifier (SUMO)-targeted ubiquitin ligases (STUbLs), which directly connect sumoylation and ubiquitylation, has been discovered. Uniquely, STUbLs use SUMO-interaction motifs (SIMs) to recognize their sumoylated targets. STUbLs are global regulators of protein sumoylation levels, and cells lacking STUbLs display genomic instability and hypersensitivity to genotoxic stress. The human STUbL, RNF4, is implicated in several diseases including cancer, highlighting the importance of characterizing the cellular functions of STUbLs.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acid Sequence
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Neoplasm Proteins / physiology
  • Nuclear Proteins / physiology
  • Proteasome Endopeptidase Complex / physiology
  • Protein Interaction Domains and Motifs
  • Saccharomycetales / physiology
  • Sequence Alignment
  • Small Ubiquitin-Related Modifier Proteins / physiology*
  • Ubiquitin / physiology*
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitin-Protein Ligases / physiology


  • Neoplasm Proteins
  • Nuclear Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitin
  • TOPORS protein, human
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex