2024
Yeast 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 ResearchMeSH KeywordsActive Transport, Cell NucleusAdaptor Proteins, Signal TransducingAlpha KaryopherinsBeta KaryopherinsGlucoseKaryopherinsProteasome Endopeptidase ComplexSaccharomyces cerevisiaeSaccharomycetalesUbiquitinConceptsProteasome 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
2001
Unraveling the means to the end in ATP-dependent proteases
Hochstrasser M, Wang J. Unraveling the means to the end in ATP-dependent proteases. Nature Structural & Molecular Biology 2001, 8: 294-296. PMID: 11276243, DOI: 10.1038/86153.Peer-Reviewed Original Research
2000
The Doa4 Deubiquitinating Enzyme Is Functionally Linked to the Vacuolar Protein-sorting and Endocytic Pathways
Amerik A, Nowak J, Swaminathan S, Hochstrasser M. The Doa4 Deubiquitinating Enzyme Is Functionally Linked to the Vacuolar Protein-sorting and Endocytic Pathways. Molecular Biology Of The Cell 2000, 11: 3365-3380. PMID: 11029042, PMCID: PMC14998, DOI: 10.1091/mbc.11.10.3365.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAmino Acid SequenceBreast NeoplasmsCysteine EndopeptidasesEndocytosisEndopeptidasesEndosomal Sorting Complexes Required for TransportFemaleFungal ProteinsGenotypeHumansMolecular Sequence DataMultienzyme ComplexesMutagenesisProteasome Endopeptidase ComplexRecombinant ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSequence Homology, Amino AcidSubstrate SpecificitySuppression, GeneticUbiquitin ThiolesteraseUbiquitinsVacuolesConceptsPrevacuolar compartmentDeubiquitinating enzymeVacuolar protein sorting (VPS) pathwayFluorescent proteinEndomembrane protein traffickingProtein sorting pathwaysUbiquitinated membrane proteinsVacuolar protein sortingClass E compartmentSpontaneous extragenic suppressorsGreen fluorescent proteinExtragenic suppressorsProtein sortingProtein traffickingProtein deubiquitinationUbiquitin recyclingPathway substrateE compartmentMembrane proteinsEndocytic pathwayUbiquitinated intermediatesDifferent genesMultivesicular bodiesNuclear distributionUnanticipated connections
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 functionsSubunitsStructure and functional analyses of the 26S proteasome subunits from plants – Plant 26S proteasome
Fu H, Girod P, Doelling J, van Nocker S, Hochstrasser M, Finley D, Vierstra R. Structure and functional analyses of the 26S proteasome subunits from plants – Plant 26S proteasome. Molecular Biology Reports 1999, 26: 137-146. PMID: 10363660, DOI: 10.1023/a:1006926322501.Peer-Reviewed Original ResearchMeSH KeywordsArabidopsisBryopsidaPeptide HydrolasesProteasome Endopeptidase ComplexStructure-Activity RelationshipConceptsProteasome degrades ubiquitinated proteinsUbiquitin fusion degradation (UFD) pathwayStructure/function analysisAAA-ATPase subunitsC-terminal motifDegradation of proteinsRegulatory particle subunitsCore particlesPlant 26SRpn10 geneArabidopsis genesYeast counterpartMoss PhyscomitrellaArabidopsis thalianaPlant hormonesUbiquitin systemProteasome genesDevelopmental programHomologous recombinationProteolytic complexPlant subunitsReverse geneticsUbiquitinated proteinsUbiquitin conjugatesVivo functionInteraction 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
A Deubiquitinating Enzyme That Disassembles Free Polyubiquitin Chains Is Required for Development but Not Growth in Dictyostelium *
Lindsey D, Amerik A, Deery W, Bishop J, Hochstrasser M, Gomer R. A Deubiquitinating Enzyme That Disassembles Free Polyubiquitin Chains Is Required for Development but Not Growth in Dictyostelium *. Journal Of Biological Chemistry 1998, 273: 29178-29187. PMID: 9786928, DOI: 10.1074/jbc.273.44.29178.Peer-Reviewed Original ResearchConceptsUbiquitin polymersPolyubiquitin chainsUbiquitin chainsDeubiquitinating enzymeCross-species complementationFree ubiquitin chainsSpecific developmental transitionsWild-type cellsFree polyubiquitin chainsNormal protein profilesDictyostelium developmentFunctional homologSequence similarityCAMP receptorNew proteinsProtein degradationAdhesion proteinsWild typeDevelopmental transitionsSpecific proteinsExogenous cAMPCell differentiationProtein profilesSpecificity assaysCell adhesionDegradation Signal Masking by Heterodimerization of MATα2 and MATa1 Blocks Their Mutual Destruction by the Ubiquitin-Proteasome Pathway
Johnson P, Swanson R, Rakhilina L, Hochstrasser M. Degradation Signal Masking by Heterodimerization of MATα2 and MATa1 Blocks Their Mutual Destruction by the Ubiquitin-Proteasome Pathway. Cell 1998, 94: 217-227. PMID: 9695950, DOI: 10.1016/s0092-8674(00)81421-x.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCysteine EndopeptidasesDimerizationDiploidyFungal ProteinsHaploidyIntramolecular TransferasesLipoproteinsMating FactorMolecular Sequence DataMultienzyme ComplexesMutationPeptidesPheromonesProteasome Endopeptidase ComplexProtein Structure, SecondarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitinsConceptsUbiquitin-proteasome pathwayDegradation signalCoiled-coil interactionsAlpha haploid cellsRegulated turnoverMultiprotein complexesHaploid cellsPathway substrateTranscription factorsExtensive mutagenesisProteolytic signalMolecular mechanismsCell typesHeterodimerizationSuch regulationCritical determinantPathwayAlpha2MATa1MATα2Signal maskingRepressorHaploidsSaccharomycesMutagenesisUnified nomenclature for subunits of the Saccharomyces cerevisiae proteasome regulatory particle
Finley D, Tanaka K, Mann C, Feldmann H, Hochstrasser M, Vierstra R, Johnston S, Hampton R, Haber J, McCusker J, Silver P, Frontali L, Thorsness P, Varshavsky A, Byers B, Madura K, Reed S, Wolf D, Jentsch S, Sommer T, Baumeister W, Goldberg A, Fried V, Rubin D, Glickman M, Toh-e A. Unified nomenclature for subunits of the Saccharomyces cerevisiae proteasome regulatory particle. Trends In Biochemical Sciences 1998, 23: 244-245. PMID: 9697412, DOI: 10.1016/s0968-0004(98)01222-5.Peer-Reviewed Original ResearchAnimalsCysteine EndopeptidasesHumansMultienzyme ComplexesProteasome Endopeptidase ComplexProtein ConformationSaccharomyces cerevisiaeTerminology as TopicMolecular 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
In 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 ResearchMeSH KeywordsBinding SitesCysteine EndopeptidasesMultienzyme ComplexesProteasome Endopeptidase ComplexSaccharomyces cerevisiaeStructure-Activity RelationshipSubstrate SpecificityConceptsActive 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 ResearchMeSH KeywordsAmino Acid SequenceCysteine EndopeptidasesHydrolysisMolecular Sequence DataMultienzyme ComplexesProteasome Endopeptidase ComplexProteinsSequence Homology, Amino AcidUbiquitinsConceptsRegulatory 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 peptidesProteinDeubiquitinationAutocatalytic Subunit Processing Couples Active Site Formation in the 20S Proteasome to Completion of Assembly
Chen P, Hochstrasser M. Autocatalytic Subunit Processing Couples Active Site Formation in the 20S Proteasome to Completion of Assembly. Cell 1996, 86: 961-972. PMID: 8808631, DOI: 10.1016/s0092-8674(00)80171-3.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsCysteine EndopeptidasesFungal ProteinsHomeodomain ProteinsMultienzyme ComplexesMutationProteasome Endopeptidase ComplexRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsConceptsSpecific regulatory proteinsMulti-subunit proteaseSelective protein turnoverCell cycle progressionPolypeptide ubiquitinTranscriptional regulatorsCellular proteinsRegulatory proteinsCellular phenomenaCovalent ligationCycle progressionIntracellular proteolysisProtein turnoverProteasomeCell growthRapid degradationMajor mechanismProteinRepressorUbiquitinVivoDegradationRegulatorProteolysisProtease
1992
Ubiquitin and intracellular protein degradation
Hochstrasser M. Ubiquitin and intracellular protein degradation. Current Opinion In Cell Biology 1992, 4: 1024-1031. PMID: 1336669, DOI: 10.1016/0955-0674(92)90135-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHumansLigasesPeptide HydrolasesProteasome Endopeptidase ComplexProteinsSignal TransductionUbiquitinsConceptsEukaryotic cell regulationConjugation of ubiquitinUbiquitin systemProteolytic targetingProtein degradationIntracellular proteinsProtein turnoverCell regulationDiverse arrayUbiquitinCentral roleProteinEukaryotesMajor routeUbiquitinationProteaseEnzymeDegradationPathwayRegulationRecent workTargetingTurnoverPeptides