A new protease required for cell-cycle progression in yeast

Nature. 1999 Mar 18;398(6724):246-51. doi: 10.1038/18457.


In eukaryotes, protein function can be modulated by ligation to ubiquitin or to ubiquitin-like proteins (Ubl proteins). The vertebrate Ubl protein SUMO-1 is only 18% identical to ubiquitin but is 48% identical to the yeast protein Smt3. Both SUMO-1 and Smt3 are ligated to cellular proteins, and protein conjugation to SUMO-1/Smt3 is involved in many physiological processes. It remained unknown, however, whether deconjugation of SUMO-1/Smt3 from proteins is also essential. Here we describe a yeast Ubl-specific protease, Ulp1, which cleaves proteins from Smt3 and SUMO-1 but not from ubiquitin. Ulp1 is unrelated to any known deubiquitinating enzyme but shows distant similarity to certain viral proteases, indicating the existence of a widely conserved protease fold. Proteins related to Ulp1 are present in many organisms, including several human pathogens. The pattern of Smt3-coupled proteins in yeast changes markedly throughout the cell cycle, and specific conjugates accumulate in ulp1 mutants. Ulp1 has several functions, including an essential role in the G2/M phase of the cell cycle.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / isolation & purification
  • Cell Cycle Proteins / metabolism*
  • Cloning, Molecular
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / isolation & purification
  • Cysteine Endopeptidases / metabolism*
  • Escherichia coli
  • Fungal Proteins / isolation & purification
  • Fungal Proteins / metabolism
  • G2 Phase / physiology
  • Humans
  • Mitosis / physiology
  • Molecular Sequence Data
  • Mutagenesis
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / metabolism
  • SUMO-1 Protein
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Small Ubiquitin-Related Modifier Proteins
  • Substrate Specificity
  • Ubiquitins / metabolism


  • Carrier Proteins
  • Cell Cycle Proteins
  • Fungal Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • SMT3 protein, S cerevisiae
  • SUMO-1 Protein
  • SUMO2 protein, human
  • Saccharomyces cerevisiae Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitins
  • Cysteine Endopeptidases
  • Ulp1 protease

Associated data

  • GENBANK/U37457
  • GENBANK/U37458