Gene Symbol: ULP2
Description: SUMO protease ULP2
Alias: SMT4, SUMO protease ULP2
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Li S, Hochstrasser M. The yeast ULP2 (SMT4) gene encodes a novel protease specific for the ubiquitin-like Smt3 protein. Mol Cell Biol. 2000;20:2367-77 pubmed
    ..We show here that SMT4 encodes an Smt3-deconjugating enzyme, Ulp2. In cells lacking Ulp2, specific Smt3-protein conjugates accumulate, and the conjugate pattern is distinct from ..
  2. Li S, Hochstrasser M. The Ulp1 SUMO isopeptidase: distinct domains required for viability, nuclear envelope localization, and substrate specificity. J Cell Biol. 2003;160:1069-81 pubmed
    ..Of its two known desumoylating enzymes, Ubl-specific protease (Ulp)1 and Ulp2/Smt4, Ulp1 is specifically required for cell cycle progression...
  3. Bachant J, Alcasabas A, Blat Y, Kleckner N, Elledge S. The SUMO-1 isopeptidase Smt4 is linked to centromeric cohesion through SUMO-1 modification of DNA topoisomerase II. Mol Cell. 2002;9:1169-82 pubmed
    ..We find that one function associated with the Smt3/SUMO-1 isopeptidase Smt4 is to control chromosome cohesion at centromeric regions and that a key Smt3/SUMO-1 substrate underlying this ..
  4. Bylebyl G, Belichenko I, Johnson E. The SUMO isopeptidase Ulp2 prevents accumulation of SUMO chains in yeast. J Biol Chem. 2003;278:44113-20 pubmed
    ..However, mutants lacking the SUMO-specific isopeptidase Ulp2 accumulated high molecular weight SUMO-containing species, which formed only when the N-terminal lysines of SUMO ..
  5. Schwartz D, Felberbaum R, Hochstrasser M. The Ulp2 SUMO protease is required for cell division following termination of the DNA damage checkpoint. Mol Cell Biol. 2007;27:6948-61 pubmed
    ..Here we show that the SUMO protease Ulp2 is required for resumption of cell division following DNA damage-induced arrest in Saccharomyces cerevisiae, ..
  6. Uzunova K, Göttsche K, Miteva M, Weisshaar S, Glanemann C, Schnellhardt M, et al. Ubiquitin-dependent proteolytic control of SUMO conjugates. J Biol Chem. 2007;282:34167-75 pubmed
    ..Simultaneous inhibition of both mechanisms leads to severe phenotypic defects. ..
  7. Baldwin M, Julius J, Tang X, Wang Y, Bachant J. The yeast SUMO isopeptidase Smt4/Ulp2 and the polo kinase Cdc5 act in an opposing fashion to regulate sumoylation in mitosis and cohesion at centromeres. Cell Cycle. 2009;8:3406-19 pubmed
    ..evidence that in budding yeast sumoylation during mitosis may be controlled through the SUMO deconjugating enzyme Smt4/Ulp2...
  8. Li S, Hochstrasser M. A new protease required for cell-cycle progression in yeast. Nature. 1999;398:246-51 pubmed
    ..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. ..
  9. Felberbaum R, Hochstrasser M. Ulp2 and the DNA damage response: desumoylation enables safe passage through mitosis. Cell Cycle. 2008;7:52-6 pubmed
    ..We recently reported that Ulp2, a SUMO protease, is required for cell division following termination of the DNA damage checkpoint in budding yeast...

More Information


  1. Stead K, Aguilar C, Hartman T, Drexel M, Meluh P, Guacci V. Pds5p regulates the maintenance of sister chromatid cohesion and is sumoylated to promote the dissolution of cohesion. J Cell Biol. 2003;163:729-41 pubmed
    ..We identified SMT4, which encodes a SUMO isopeptidase, as a high copy suppressor of both the temperature sensitivity and precocious ..
  2. D Amours D, Stegmeier F, Amon A. Cdc14 and condensin control the dissolution of cohesin-independent chromosome linkages at repeated DNA. Cell. 2004;117:455-69 pubmed
    ..This dual role of the FEAR network in initiating mitotic exit and promoting chromosome segregation ensures that exit from mitosis is coupled to the completion of chromosome segregation. ..
  3. Schwienhorst I, Johnson E, Dohmen R. SUMO conjugation and deconjugation. Mol Gen Genet. 2000;263:771-86 pubmed
    ..uha2-ts9, we isolated a strain with a null mutation (sut9) in a gene of hitherto unknown function (SUT9/YIL031W/SMT4)...
  4. Kroetz M, Su D, Hochstrasser M. Essential role of nuclear localization for yeast Ulp2 SUMO protease function. Mol Biol Cell. 2009;20:2196-206 pubmed publisher
    ..This modification is rapidly reversed by SUMO proteases. The Saccharomyces cerevisiae SUMO protease Ulp2 is a nuclear protein required for chromosome stability and cell cycle restart after checkpoint arrest...
  5. Strunnikov A, Aravind L, Koonin E. Saccharomyces cerevisiae SMT4 encodes an evolutionarily conserved protease with a role in chromosome condensation regulation. Genetics. 2001;158:95-107 pubmed
    ..complex to chromatin in Saccharomyces cerevisiae, we identified a member of the adenovirus protease family, SMT4. SMT4 overexpression suppresses the temperature-sensitive conditional lethal phenotype of smc2-6, but not smc2-8 or ..
  6. Jacquiau H, van Waardenburg R, Reid R, Woo M, Guo H, Johnson E, et al. Defects in SUMO (small ubiquitin-related modifier) conjugation and deconjugation alter cell sensitivity to DNA topoisomerase I-induced DNA damage. J Biol Chem. 2005;280:23566-75 pubmed
    ..Deletion of the Ulp2 SUMO protease failed to restore ubc9-10 cell resistance to Top1p poisons or hydroxyurea yet adversely affected wild-..
  7. Darst R, Garcia S, Koch M, Pillus L. Slx5 promotes transcriptional silencing and is required for robust growth in the absence of Sir2. Mol Cell Biol. 2008;28:1361-72 pubmed
    ..A similar requirement was observed for mutants of the SUMO isopeptidase Ulp2/Smt4. The contribution of Sir2 to optimal growth was not due to known Sir2 roles in mating-type determination or rDNA ..
  8. Mullen J, Das M, Brill S. Genetic evidence that polysumoylation bypasses the need for a SUMO-targeted Ub ligase. Genetics. 2011;187:73-87 pubmed publisher
    ..we isolated a second-site suppressor of sgs1? slx5? synthetic lethality and identified it as an allele of the ULP2 SUMO isopeptidase...
  9. Felberbaum R, Wilson N, Cheng D, Peng J, Hochstrasser M. Desumoylation of the endoplasmic reticulum membrane VAP family protein Scs2 by Ulp1 and SUMO regulation of the inositol synthesis pathway. Mol Cell Biol. 2012;32:64-75 pubmed publisher
    ..Mutants lacking the Ulp2 SUMO protease are the most severely affected, and this defect was traced to the mutants' impaired ability to induce ..
  10. Eckhoff J, Dohmen R. In Vitro Studies Reveal a Sequential Mode of Chain Processing by the Yeast SUMO (Small Ubiquitin-related Modifier)-specific Protease Ulp2. J Biol Chem. 2015;290:12268-81 pubmed publisher
    ..In Saccharomyces cerevisiae there are apparently only two SUMO(Smt3)-specific proteases: Ulp1 and Ulp2. Ulp2 has been shown to be important for the control of poly-SUMO conjugates in cells and to dismantle SUMO chains ..
  11. Craven R, Petes T. Involvement of the checkpoint protein Mec1p in silencing of gene expression at telomeres in Saccharomyces cerevisiae. Mol Cell Biol. 2000;20:2378-84 pubmed
    ..In addition, the loss of telomeric silencing in mec1 strains was not a consequence of the slightly shortened telomeres observed in these strains. ..
  12. Lee M, Bakir A, Nguyen K, Bachant J. The SUMO isopeptidase Ulp2p is required to prevent recombination-induced chromosome segregation lethality following DNA replication stress. PLoS Genet. 2011;7:e1001355 pubmed publisher
    ..We find that spontaneous recombination is elevated in ulp2 strains and that recombination DNA repair is essential for ulp2 survival...
  13. Wysocka M, Rytka J, Kurlandzka A. Saccharomyces cerevisiae CSM1 gene encoding a protein influencing chromosome segregation in meiosis I interacts with elements of the DNA replication complex. Exp Cell Res. 2004;294:592-602 pubmed
    ..Three other interacting proteins, Mgs1p, Ulp2, and Plp2, participate in chromosome assembling and segregation, whereas the function of two others has not been ..
  14. Wang Z, Jones G, Prelich G. Genetic analysis connects SLX5 and SLX8 to the SUMO pathway in Saccharomyces cerevisiae. Genetics. 2006;172:1499-509 pubmed
  15. Sharma P, Mullen J, Li M, Zaratiegui M, Bunting S, Brill S. A Lysine Desert Protects a Novel Domain in the Slx5-Slx8 SUMO Targeted Ub Ligase To Maintain Sumoylation Levels in Saccharomyces cerevisiae. Genetics. 2017;206:1807-1821 pubmed publisher
    ..lethality isolated mutations in genes known to control global sumoylation levels including ULP1, ULP2, SIZ2, and SLX5 The results suggest that alternative pathways of repair become available when ..
  16. Tan W, Wang Z, Prelich G. Physical and Genetic Interactions Between Uls1 and the Slx5-Slx8 SUMO-Targeted Ubiquitin Ligase. G3 (Bethesda). 2013;3:771-780 pubmed publisher
  17. D Ambrosio L, Lavoie B. Pds5 prevents the PolySUMO-dependent separation of sister chromatids. Curr Biol. 2014;24:361-71 pubmed publisher
    ..We propose that Pds5 maintains cohesion, at least in part, by antagonizing the polySUMO-dependent degradation of cohesin. ..
  18. Lewis A, Felberbaum R, Hochstrasser M. A nuclear envelope protein linking nuclear pore basket assembly, SUMO protease regulation, and mRNA surveillance. J Cell Biol. 2007;178:813-27 pubmed
    ..The results raise the possibility that NPC-localized protein desumoylation may be a key regulatory event preventing inappropriate pre-mRNA export. ..
  19. Tosti E, Katakowski J, Schaetzlein S, Kim H, Ryan C, Shales M, et al. Evolutionarily conserved genetic interactions with budding and fission yeast MutS identify orthologous relationships in mismatch repair-deficient cancer cells. Genome Med. 2014;6:68 pubmed publisher
    ..with MutSβ (msh2Δ/msh3Δ) were directly analyzed in budding yeast, and the CGI with SUMO-protease Ulp2 further examined after RNA interference/drug treatment in MSH2-deficient and -proficient human cells...
  20. Ryu H, Wilson N, Mehta S, Hwang S, Hochstrasser M. Loss of the SUMO protease Ulp2 triggers a specific multichromosome aneuploidy. Genes Dev. 2016;30:1881-94 pubmed publisher
    ..The SUMO protease Ulp2 modulates many of these SUMO-dependent processes in budding yeast...
  21. Mullen J, Chen C, Brill S. Wss1 is a SUMO-dependent isopeptidase that interacts genetically with the Slx5-Slx8 SUMO-targeted ubiquitin ligase. Mol Cell Biol. 2010;30:3737-48 pubmed publisher
    ..The results suggest that Wss1 is a SUMO-dependent isopeptidase that acts on sumoylated substrates as they undergo proteasomal degradation. ..
  22. Gillies J, Hickey C, Su D, Wu Z, Peng J, Hochstrasser M. SUMO Pathway Modulation of Regulatory Protein Binding at the Ribosomal DNA Locus in Saccharomyces cerevisiae. Genetics. 2016;202:1377-94 pubmed publisher
    In this report, we identify cellular targets of Ulp2, one of two Saccharomyces cerevisiae small ubiquitin-related modifier (SUMO) proteases, and investigate the function of SUMO modification of these proteins...
  23. Snead J, Sullivan M, Lowery D, Cohen M, Zhang C, Randle D, et al. A coupled chemical-genetic and bioinformatic approach to Polo-like kinase pathway exploration. Chem Biol. 2007;14:1261-72 pubmed
    ..Finally, an examination of Cdc5 binding by SPB-localized proteins expanded our knowledge of Cdc5 function at the SPB. ..
  24. Eckhoff J, Dohmen R. In Vitro Characterization of Chain Depolymerization Activities of SUMO-Specific Proteases. Methods Mol Biol. 2016;1475:123-35 pubmed publisher
    ..cerevisiae Ulp enzymes in crude extract from E. coli. This fast and economic approach should be applicable to SUMO-specific proteases from other species as well. ..
  25. Psakhye I, Jentsch S. Protein group modification and synergy in the SUMO pathway as exemplified in DNA repair. Cell. 2012;151:807-820 pubmed publisher
    ..We propose that SUMOylation may thus often target a protein group rather than individual proteins, whereas localized modification enzymes and highly specific triggers ensure specificity. ..
  26. Thu Y, Van Riper S, Higgins L, Zhang T, Becker J, Markowski T, et al. Slx5/Slx8 Promotes Replication Stress Tolerance by Facilitating Mitotic Progression. Cell Rep. 2016;15:1254-65 pubmed publisher
    ..Based on these findings, we propose a model in which Slx5/8 allows for passage through mitosis when replication stress is tolerable. ..
  27. Rothenbusch U, Sawatzki M, Chang Y, Caesar S, Schlenstedt G. Sumoylation regulates Kap114-mediated nuclear transport. EMBO J. 2012;31:2461-72 pubmed publisher
    ..Remarkably, sumoylation of Kap114 greatly stimulates cargo dissociation in vitro. We propose that sumoylation occurs at the site of Kap114 cargo function and that SUMO is a cargo release factor involved in intranuclear targeting. ..
  28. Abu Irqeba A, Li Y, Panahi M, Zhu M, Wang Y. Regulating global sumoylation by a MAP kinase Hog1 and its potential role in osmo-tolerance in yeast. PLoS ONE. 2014;9:e87306 pubmed publisher