Modification in reverse: the SUMO proteases

Trends Biochem Sci. 2007 Jun;32(6):286-95. doi: 10.1016/j.tibs.2007.05.002. Epub 2007 May 17.


SUMOs (small ubiquitin-like modifiers) are ubiquitin-related proteins that become covalently conjugated to cellular target proteins that are involved in a variety of processes. Frequently, this modification has a key role in regulating the activities of those targets and, thus, their cellular functions. SUMO conjugation is a highly dynamic process that can be rapidly reversed by the action of members of the Ubl (ubiquitin-like protein)-specific protease (Ulp) family. The same family of enzymes is also responsible for maturation of newly synthesized SUMOs prior to their initial conjugation. Recent advances in structural, biochemical and cell biological analysis of Ulp/SENPs reveal their high degree of specificity towards SUMO paralogs, in addition to discrimination between processing, deconjugation and chain-editing reactions. The dissimilar sub-nuclear localization patterns of Ulp/SENPs and phenotypes of Ulp/SENP mutants further indicate that different Ulp/SENPs have distinct and non-redundant roles.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / physiology*
  • Endopeptidases / genetics
  • Endopeptidases / physiology
  • Evolution, Molecular
  • Gene Expression Regulation
  • Humans
  • Models, Biological
  • Peptide Hydrolases / physiology
  • Protein Transport / physiology
  • Repressor Proteins / physiology
  • Saccharomyces cerevisiae Proteins / physiology
  • Small Ubiquitin-Related Modifier Proteins / physiology*
  • Ubiquitins / physiology*


  • Repressor Proteins
  • SMT3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitins
  • Endopeptidases
  • Peptide Hydrolases
  • Senp5 protein, human
  • Cysteine Endopeptidases
  • SENP2 protein, human
  • SENP6 protein, human
  • Senp1 protein, mouse
  • Ulp1 protease