2024
Limiting 20S proteasome assembly leads to unbalanced nucleo-cytoplasmic distribution of 26S/30S proteasomes and chronic proteotoxicity
Ruiz-Romero G, Berdún M, Hochstrasser M, Salas-Pino S, Daga R. Limiting 20S proteasome assembly leads to unbalanced nucleo-cytoplasmic distribution of 26S/30S proteasomes and chronic proteotoxicity. IScience 2024, 27: 111095. PMID: 39473973, PMCID: PMC11513537, DOI: 10.1016/j.isci.2024.111095.Peer-Reviewed Original ResearchProteasome assemblyDegradation of cell cycle proteinsNucleo-cytoplasmic distributionCell cycle proteinsHeat shock responseCytoplasmic proteostasisFission yeastMitotic substratesProteasome regulationCytoplasmic aggregatesUnfolded proteinsProteasome activityProteasomeConstitutive activationFunctional relevanceShock responseUmp1Cell proliferationProteinCellsCompartmentalizationAssemblyProteostasisYeastChaperoneYeast 26S proteasome nuclear import is coupled to nucleus-specific degradation of the karyopherin adaptor protein Sts1
Breckel C, Johnson Z, Hickey C, Hochstrasser M. Yeast 26S proteasome nuclear import is coupled to nucleus-specific degradation of the karyopherin adaptor protein Sts1. Scientific Reports 2024, 14: 2048. PMID: 38267508, PMCID: PMC10808114, DOI: 10.1038/s41598-024-52352-5.Peer-Reviewed Original ResearchConceptsProteasome storage granulesNuclear importUbiquitin-independent proteasomal degradationProteasome degradation in vitroYeast Saccharomyces cerevisiaeProlonged glucose starvationNuclear import factorsUbiquitin-proteasome systemProteasome interactionGlucose starvationKaryopherin proteinsProteasomal degradationNuclear transportCellular homeostasisDegradation in vivoSTS1KaryopherinProtein degradationProteasomeDegradation in vitroGlucose refeedingStorage granulesProteinEukaryotesRanGTP
2023
Proteasomes: Isolation and Activity Assays
Li Y, Tomko R, Hochstrasser M. Proteasomes: Isolation and Activity Assays. Current Protocols 2023, 3: e717. PMID: 37026813, PMCID: PMC10337785, DOI: 10.1002/cpz1.717.Peer-Reviewed Original ResearchConceptsRegulatory particleOne-step purification schemeCore particlesMultisubunit protease complexUbiquitin-proteasome systemUbiquitin polypeptidesUnneeded proteinsYeast SaccharomycesProtein substratesProtease complexProteasomeGel filtration stepPurification schemeProteolytic activityEukaryotesSaccharomycesPolypeptideProteinSubstrateAssaysComplexes
2022
Orientia tsutsugamushi OtDUB Is Expressed and Interacts with Adaptor Protein Complexes during Infection
Adcox H, Berk J, Hochstrasser M, Carlyon J. Orientia tsutsugamushi OtDUB Is Expressed and Interacts with Adaptor Protein Complexes during Infection. Infection And Immunity 2022, 90: e00469-22. PMID: 36374099, PMCID: PMC9753657, DOI: 10.1128/iai.00469-22.Peer-Reviewed Original ResearchConceptsObligate intracellular lifestyleClathrin adaptor protein complex 1Adaptor protein complex 1Non-integral membrane proteinsAdaptor protein complexesHost endocytic pathwayMembrane traffic regulatorsCell wall proteinsWall proteinsProtein complexesIntracellular lifestyleRho GTPasesAdapter proteinEndocytic pathwayMembrane proteinsUbiquitin bindingCellular pathwaysCell wallStructured illumination microscopyPhospholipid phosphatidylserineIntact bacteriaO. tsutsugamushi infectionProteinRecombinant versionInteractome
2020
The Relationship between ER Stress and Protein Quality Control at the Translocon
Broshar C, Buchanan B, Mehrtash A, Runnebohm A, Snow B, Scanameo L, Hochstrasser M, Rubenstein E. The Relationship between ER Stress and Protein Quality Control at the Translocon. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.00497.Peer-Reviewed Original ResearchProtein quality controlUbiquitin-proteasome systemER stressUbiquitin ligaseDegradation signalProtein quality control mechanismsHrd1 ubiquitin ligaseTranslocon-associated proteinLipid homeostasisStress-sensing mechanismsStress-responsive mechanismsQuality control mechanismsDegradation of proteinsERAD pathwayModel organismsEndoplasmic reticulum stressProtein misfoldingAberrant proteinsERADImpairs degradationProtein degradationProteins misfoldHeat shockEndoplasmic reticulumProtein
2013
Chapter 462 The Doa4 Deubiquitylating Enzyme (Saccharomyces cerevisiae)
Amerik A, Hochstrasser M. Chapter 462 The Doa4 Deubiquitylating Enzyme (Saccharomyces cerevisiae). 2013, 2049-2052. DOI: 10.1016/b978-0-12-382219-2.00461-0.Peer-Reviewed Original ResearchChapter 528 Ulp2 SUMO Protease
Gillies J, Su D, Hochstrasser M. Chapter 528 Ulp2 SUMO Protease. 2013, 2362-2365. DOI: 10.1016/b978-0-12-382219-2.00526-3.Peer-Reviewed Original Research
2008
Ubiquitin and Ubiquitin‐like Protein Conjugation
Hochstrasser M. Ubiquitin and Ubiquitin‐like Protein Conjugation. 2008, 249-278. DOI: 10.1002/9783527610754.mr02.Peer-Reviewed Original ResearchEukaryotic cell regulationR. John MayerUbiquitin-like proteinConjugation systemAaron CiechanoverEvolutionary originMartin RechsteinerMost ubiquitinUbl systemsProtein modifiersProtein modificationProtein degradationBiological processesUbiquitinCell regulationMacromolecular interactionsRelated enzymesEnormous arrayProteinDistinct mechanismsConjugated proteinsFunctional featuresRapid degradationPervasive roleJohn Mayer
2003
Chapter 181 The Ubiquitin-Proteasome System
Hochstrasser M. Chapter 181 The Ubiquitin-Proteasome System. 2003, 347-350. DOI: 10.1016/b978-012124546-7/50542-8.Peer-Reviewed Original ResearchUbiquitin-proteasome systemProtein ubiquitinationMembrane proteinsFunction of ubiquitinUbiquitin-dependent proteolysisCellular regulatory mechanismsCell cycle controlSignal transduction pathwaysNegative cell cycle regulatorsCell cycle regulatorsKey regulatory pathwaysSubstrate proteinsMitotic exitProtein phosphorylationTransduction pathwaysRegulatory pathwaysC-terminusCycle controlRegulatory mechanismsIntracellular proteinsCell cycleUbiquitinationTimed degradationProteinUbiquitin
2001
SP-RING for SUMO New Functions Bloom for a Ubiquitin-like Protein
Hochstrasser M. SP-RING for SUMO New Functions Bloom for a Ubiquitin-like Protein. Cell 2001, 107: 5-8. PMID: 11595179, DOI: 10.1016/s0092-8674(01)00519-0.Peer-Reviewed Original Research
2000
Evolution and function of ubiquitin-like protein-conjugation systems
Hochstrasser M. Evolution and function of ubiquitin-like protein-conjugation systems. Nature Cell Biology 2000, 2: e153-e157. PMID: 10934491, DOI: 10.1038/35019643.Peer-Reviewed Original ResearchA viable ubiquitin‐activating enzyme mutant for evaluating ubiquitin system function in Saccharomyces cerevisiae
Swanson R, Hochstrasser M. A viable ubiquitin‐activating enzyme mutant for evaluating ubiquitin system function in Saccharomyces cerevisiae. FEBS Letters 2000, 477: 193-198. PMID: 10908719, DOI: 10.1016/s0014-5793(00)01802-0.Peer-Reviewed Original ResearchConceptsUbiquitin system functionActivation of ubiquitinUbiquitin-activating enzymeProteasome-independent degradationUbiquitin systemCellular processesPathway substrateMammalian cellsHypomorphic alleleProtein modificationEnzyme mutantsMutant allelesMembrane receptorsMutantsUbiquitinComparable mutantsSaccharomycesCell functionAllelesProteasomeYeastProteinEnzymeDegradationE1The Yeast ULP2 (SMT4) Gene Encodes a Novel Protease Specific for the Ubiquitin-Like Smt3 Protein
Li S, Hochstrasser M. The Yeast ULP2 (SMT4) Gene Encodes a Novel Protease Specific for the Ubiquitin-Like Smt3 Protein. Molecular And Cellular Biology 2000, 20: 2367-2377. PMID: 10713161, PMCID: PMC85410, DOI: 10.1128/mcb.20.7.2367-2377.2000.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell DivisionChromosomesCysteine EndopeptidasesDNA DamageEndopeptidasesFungal ProteinsHydroxyureaMitosisMolecular Sequence DataMutationRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidSmall Ubiquitin-Related Modifier ProteinsSUMO-1 ProteinTemperatureUbiquitinsConceptsCell cycle checkpoint arrestTemperature-sensitive growthCentromere-binding proteinsUbiquitin-like proteinDNA-damaging agentsAbnormal cell morphologyYeast SMT3Number suppressorGene EncodesPleiotropic phenotypesChromosome stabilityMutant accumulatesSingle mutantsCheckpoint arrestUlp2SUMO-1Smt3Ulp1DNA damageMutantsReplication inhibitionProteinCell morphologyNormal kineticsCell function
1999
The Doa4 Deubiquitinating Enzyme Is Required for Ubiquitin Homeostasis in Yeast
Swaminathan S, Amerik A, Hochstrasser M. The Doa4 Deubiquitinating Enzyme Is Required for Ubiquitin Homeostasis in Yeast. Molecular Biology Of The Cell 1999, 10: 2583-2594. PMID: 10436014, PMCID: PMC25490, DOI: 10.1091/mbc.10.8.2583.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCytoskeletal ProteinsEndopeptidasesEndosomal Sorting Complexes Required for TransportFungal ProteinsHomeostasisMutationPeptide HydrolasesProteasome Endopeptidase ComplexSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitin ThiolesteraseUbiquitinsVacuolesVesicular Transport ProteinsConceptsDeubiquitinating enzymeAttachment of ubiquitinUbiquitin-dependent proteolysisYeast Saccharomyces cerevisiaeWild-type cellsCell surface proteinsAdditional ubiquitinVacuolar proteolysisUbiquitinated substratesUbiquitin homeostasisCellular proteinsMembrane proteinsUbiquitinated intermediatesSaccharomyces cerevisiaeGenetic dataDoa4Loss of viabilityUbiquitin depletionUbiquitinProteolytic intermediatesProteasomeSurface proteinsUbiquitin degradationEventual degradationProteinA new protease required for cell-cycle progression in yeast
Li S, Hochstrasser M. A new protease required for cell-cycle progression in yeast. Nature 1999, 398: 246-251. PMID: 10094048, DOI: 10.1038/18457.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCell Cycle ProteinsCloning, MolecularCysteine EndopeptidasesEscherichia coliFungal ProteinsG2 PhaseHumansMitosisMolecular Sequence DataMutagenesisRecombinant Fusion ProteinsRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidSmall Ubiquitin-Related Modifier ProteinsSubstrate SpecificitySUMO-1 ProteinUbiquitinsConceptsSUMO-1Cell cycleUbl-specific proteasesUbiquitin-like proteinCell cycle progressionG2/M phaseProtein functionSmt3Cellular proteinsDeubiquitinating enzymeUlp1Distant similarityUbiquitinHuman pathogensM phaseProteinEssential roleNew proteaseProteaseViral proteaseProtein conjugationEukaryotesMutantsUBLYeast
1998
The Deubiquitinating Enzymes
Wilkinson K, Hochstrasser M. The Deubiquitinating Enzymes. 1998, 99-125. DOI: 10.1007/978-1-4899-1922-9_4.Peer-Reviewed Original ResearchPolyubiquitin chainsTypes of ubiquitinationReceptor-mediated signal transductionCell cycle progressionModification of proteinsOrganelle biogenesisUbiquitin polypeptidesChromosome structureUbiquitin moleculesCellular processesProtein localizationSignal transductionDeubiquitinating enzymeIsopeptide linkageLysine 48Lysine 6C-terminusGene expressionIsopeptide bondsStress responseUbiquitinProteinProtein metabolismViral pathogenesisBiogenesisUbiquitin-Dependent Degradation of Transcription Regulators
Hochstrasser M, Kornitzer D. Ubiquitin-Dependent Degradation of Transcription Regulators. 1998, 279-302. DOI: 10.1007/978-1-4899-1922-9_9.Peer-Reviewed Original ResearchTranscription factorsTranscription regulatorsBacterial transcription factorsYeast transcription factorUbiquitin-dependent degradationUbiquitin-proteasome pathwayActivity of proteinsTranscription factor c-FosMain regulatory proteinTranscription initiationCellular proteinsRegulatory proteinsC-MycProteinMost cellsRegulatorIntracellular levelsExamples of degradationC-fosRapid modulationPathwayNumerous levelsEukaryotesMATα2Σ32
1997
SUMO-1: Ubiquitin gains weight
Johnson P, Hochstrasser M. SUMO-1: Ubiquitin gains weight. Trends In Cell Biology 1997, 7: 408-413. PMID: 17708991, DOI: 10.1016/s0962-8924(97)01132-x.Peer-Reviewed Original ResearchNuclear pore complexUbiquitin-like proteinNucleocytoplasmic traffickingPore complexUbiquitin systemPolypeptide functionsProtein crucialSUMO-1Cell biologyDistant similaritySpecific proteinsMechanistic questionsProteinSubstrate degradationProteasomeRecent findingsUbiquitinTraffickingBiologyRoleModificationCrucialComplexesSimilarityIn vivo disassembly of free polyubiquitin chains by yeast Ubp14 modulates rates of protein degradation by the proteasome
Amerik A, Swaminathan S, Krantz B, Wilkinson K, Hochstrasser M. In vivo disassembly of free polyubiquitin chains by yeast Ubp14 modulates rates of protein degradation by the proteasome. The EMBO Journal 1997, 16: 4826-4838. PMID: 9305625, PMCID: PMC1170118, DOI: 10.1093/emboj/16.16.4826.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBinding SitesCarbon-Nitrogen LyasesEndopeptidasesFungal ProteinsGene Expression Regulation, FungalGenes, FungalHumansImmunoblottingLyasesMolecular Sequence DataMutagenesis, Site-DirectedPeptide HydrolasesPhenotypeProteasome Endopeptidase ComplexProtein BindingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSubstrate SpecificityUbiquitinsConceptsUnanchored ubiquitin chainsUbiquitin chainsProtein degradationFree ubiquitin chainsUbiquitin-dependent proteolysisWild-type cellsActive site mutantsFree polyubiquitin chainsEukaryotic proteinsFunctional homologComplementation analysisPolyubiquitin chainsSteady-state levelsDeubiquitinating enzymeUbp14Site mutantsIsopeptidase TCellular proteasesYeast cellsProteasomeInhibition of degradationStriking accumulationProteolysisProteinCells
1996
UBIQUITIN-DEPENDENT PROTEIN DEGRADATION
Hochstrasser M. UBIQUITIN-DEPENDENT PROTEIN DEGRADATION. Annual Review Of Genetics 1996, 30: 405-439. PMID: 8982460, DOI: 10.1146/annurev.genet.30.1.405.Peer-Reviewed Original ResearchConceptsRegulatory mechanismsUbiquitin-dependent protein degradationLarge enzyme familyAttachment of ubiquitinCellular regulatory mechanismsSignal transduction pathwaysHigh substrate specificityReceptor-mediated endocytosisPolypeptide ubiquitinProtein ubiquitinationUbiquitin systemTransduction pathwaysEnzyme familyUbiquitinated proteinsSubstrate specificityProtein modificationProtein degradationCell cycleProteasomeUbiquitinationKey transitionsUbiquitinShort peptidesProteinDeubiquitination