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
Species-specific protein–protein interactions govern the humanization of the 20S proteasome in yeast
Sultana S, Abdullah M, Li J, Hochstrasser M, Kachroo A. Species-specific protein–protein interactions govern the humanization of the 20S proteasome in yeast. Genetics 2023, 225: iyad117. PMID: 37364278, PMCID: PMC10471208, DOI: 10.1093/genetics/iyad117.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsYeast proteasomeLocal protein-protein interactionsSpecific protein-protein interactionsYeast proteasome subunitsVast evolutionary distancesC-terminal tailFull-length tailThousands of genesHigh-throughput pipelineYeast counterpartEvolutionary divergenceEvolutionary distanceAssembly intermediatesHuman genesProteasome subunitsComplementationProteasomeSubunitsYeastGenesDistinct interactionsCore assemblyHuman β3Β3 subunitProteasomes: 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
2013
Chapter 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
2007
Biochemical Functions of Ubiquitin and Ubiquitin‐like Protein Conjugation
Hochstrasser M. Biochemical Functions of Ubiquitin and Ubiquitin‐like Protein Conjugation. 2007, 249-278. DOI: 10.1002/9783527619320.ch11a.Peer-Reviewed Original ResearchSUMO-binding motifMembrane protein traffickingUbiquitin receptorsMVB pathwayUbl conjugationGeneral biochemical functionsBiochemical functionsPositive regulationNegative regulationProtein traffickingProteasome pathwayUbiquitin-like protein conjugationProtein ubiquitinRNA virus buddingCross regulationChange interactionsModification cyclesVirus buddingUbiquitinSulfurtransferasesProteasomeMotifSUMOylationRegulationPathway
2005
Biochemical Functions of Ubiquitin and Ubiquitin‐like Protein Conjugation
Hochstrasser M. Biochemical Functions of Ubiquitin and Ubiquitin‐like Protein Conjugation. 2005, 249-278. DOI: 10.1002/9783527620210.ch11.Peer-Reviewed Original ResearchSUMO-binding motifMembrane protein traffickingUbiquitin receptorsMVB pathwayUbl conjugationGeneral biochemical functionsBiochemical functionsPositive regulationNegative regulationProtein traffickingProteasome pathwayUbiquitin-like protein conjugationProtein ubiquitinRNA virus buddingCross regulationChange interactionsModification cyclesVirus buddingUbiquitinSulfurtransferasesProteasomeMotifSUMOylationRegulationPathway
2000
A 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 functionAllelesProteasomeYeastProteinEnzymeDegradationE1
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 degradationProteinEukaryotic 20S proteasome catalytic subunit propeptides prevent active site inactivation by N‐terminal acetylation and promote particle assembly
Arendt C, Hochstrasser M. Eukaryotic 20S proteasome catalytic subunit propeptides prevent active site inactivation by N‐terminal acetylation and promote particle assembly. The EMBO Journal 1999, 18: 3575-3585. PMID: 10393174, PMCID: PMC1171436, DOI: 10.1093/emboj/18.13.3575.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAmino Acid SequenceArylamine N-AcetyltransferaseBinding SitesCatalysisCatalytic DomainCell DivisionCysteine EndopeptidasesEndopeptidasesFungal ProteinsIsoenzymesMolecular Sequence DataMultienzyme ComplexesPeptide FragmentsPhenotypeProteasome Endopeptidase ComplexSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence DeletionThreonineConceptsProteasome assemblyFirst biochemical evidenceN-terminal acetylationUbiquitin-proteasome systemProteolytic active sitesBarrel-shaped structureCatalytic threonine residueYeast 20S proteasomeThreonine residuesHeptameric ringsProteasome biogenesisEnvironmental stressNovel functionDistinct functionsLarge proteaseDifferent subunitsParticle assemblyAlpha-amino groupSpecific peptidase activityProteasomeCatalytic mechanismSite inactivationPeptidase activityCritical functionsSubunitsInteraction of the Doa4 Deubiquitinating Enzyme with the Yeast 26S Proteasome
Papa F, Amerik A, Hochstrasser M. Interaction of the Doa4 Deubiquitinating Enzyme with the Yeast 26S Proteasome. Molecular Biology Of The Cell 1999, 10: 741-756. PMID: 10069815, PMCID: PMC25199, DOI: 10.1091/mbc.10.3.741.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCysteine EndopeptidasesEndopeptidasesEndosomal Sorting Complexes Required for TransportFungal ProteinsMolecular Sequence DataMultienzyme ComplexesProteasome Endopeptidase ComplexRecombinant ProteinsSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidStructure-Activity RelationshipUbiquitin ThiolesteraseYeastsConceptsRemoval of ubiquitinUbiquitin-proteasome pathwayYeast 26S ProteasomeProteasome bindingGenetic interactionsProteasome mutationsDoa4Protein substratesCatalytic domainDeubiquitinating enzymeUbp5Physical associationProteolytic intermediatesProteasomeN-terminalFunctional interactionEnzymeRecombination methodRapid degradationMutationsPurification procedurePathwaySubstrate breakdownCopurifiesSaccharomyces
1998
Molecular Organization of the 20S Proteasome Gene Family from Arabidopsis thaliana
Fu H, Doelling J, Arendt C, Hochstrasser M, Vierstra R. Molecular Organization of the 20S Proteasome Gene Family from Arabidopsis thaliana. Genetics 1998, 149: 677-692. PMID: 9611183, PMCID: PMC1460176, DOI: 10.1093/genetics/149.2.677.Peer-Reviewed Original ResearchConceptsSubunit geneCross-species complementationCollection of cDNAsMolecular organizationAbnormal intracellular proteinsBeta-subunit geneProteasome gene familyProteasome alphaPlant ArabidopsisYeast orthologArabidopsis thalianaGenomic clonesGene familyYeast complexSingle geneUbiquitin conjugationProteolytic complexBeta polypeptideSubunit arrangementProteasome subunitsIntracellular proteinsProteasomeGenesSymmetric organizationArabidopsis
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 accumulationProteolysisProteinCellsIdentification of the yeast 20S proteasome catalytic centers and subunit interactions required for active-site formation
Arendt C, Hochstrasser M. Identification of the yeast 20S proteasome catalytic centers and subunit interactions required for active-site formation. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 7156-7161. PMID: 9207060, PMCID: PMC23776, DOI: 10.1073/pnas.94.14.7156.Peer-Reviewed Original ResearchConceptsActive siteN-terminal threonineBeta subunitDistinct peptidase activitiesMost minor effectsSubunit ringDifferent beta subunitsCorresponding threonineActive site formationUbiquitin-dependent proteolysisDegradation of substratesProteasome active sitesYeast proteasomeArchaeal proteasomeDifferent eukaryotesActive-site nucleophileUbiquitin pathwayHeptameric ringsBasic residuesSubunit interactionsAcidic residuesAlpha subunitSubstrateProteasomePeptide substrates
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
1995
Ubiquitin, proteasomes, and the regulation of intracellular protein degradation
Hochstrasser M. Ubiquitin, proteasomes, and the regulation of intracellular protein degradation. Current Opinion In Cell Biology 1995, 7: 215-223. PMID: 7612274, DOI: 10.1016/0955-0674(95)80031-x.Peer-Reviewed Original ResearchConceptsCellular regulatory mechanismsIntracellular protein degradationCell cycle progressionProtein ubiquitinationUbiquitin systemProtein degradationRegulatory mechanismsCycle progressionSpecific proteinsForeign proteinsLarge familyCell proliferationProteasomeRapid degradationProteinClass I MHC moleculesUbiquitinationDeubiquitinationUbiquitinI MHC moleculesProteolysisEnzymeKey stepDegradationRegulation
1994
Degradation of the yeast MATα2 transcriptional regulator is mediated by the proteasome
Richter-Ruoff B, Wolf D, Hochstrasser M. Degradation of the yeast MATα2 transcriptional regulator is mediated by the proteasome. FEBS Letters 1994, 354: 50-52. PMID: 7957900, DOI: 10.1016/0014-5793(94)01085-4.Peer-Reviewed Original ResearchConceptsSpecific regulatory proteinsMulti-subunit proteaseSelective protein turnoverCell cycle progressionPolypeptide ubiquitinTranscriptional regulatorsCellular proteinsRegulatory proteinsCellular phenomenaCovalent ligationCycle progressionIntracellular proteolysisProtein turnoverProteasomeCell growthRapid degradationMajor mechanismProteinRepressorUbiquitinVivoDegradationRegulatorProteolysisProtease