2023
Sis2 regulates yeast replicative lifespan in a dose-dependent manner
Ölmez T, Moreno D, Liu P, Johnson Z, McGinnis M, Tu B, Hochstrasser M, Acar M. Sis2 regulates yeast replicative lifespan in a dose-dependent manner. Nature Communications 2023, 14: 7719. PMID: 38012152, PMCID: PMC10682402, DOI: 10.1038/s41467-023-43233-y.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleCell Cycle ProteinsDNA ReplicationLongevitySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsConceptsYeast replicative lifespanReplicative lifespanRNA-seq experimentsCoenzyme A biosynthesis pathwayYeast lifespanYeast strainsStrain librariesLifespan regulationRNA-seqGene networksDose-dependent mannerLifespan extensionTranscriptional increaseYeastLifespan measurementsWild-typeGenesMachinery componentsStrainMicrofluidic platformApplications of microfluidic platformsLifespanDeletionCoenzymePathwayEctopic RING activity at the ER membrane differentially impacts ERAD protein quality control pathways
Mehrtash A, Hochstrasser M. Ectopic RING activity at the ER membrane differentially impacts ERAD protein quality control pathways. Journal Of Biological Chemistry 2023, 299: 102927. PMID: 36682496, PMCID: PMC9950527, DOI: 10.1016/j.jbc.2023.102927.Peer-Reviewed Original ResearchMeSH KeywordsEndoplasmic Reticulum-Associated DegradationGene ExpressionSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitinationUbiquitin-Protein LigasesConceptsEndoplasmic reticulum-associated degradationProtein quality control pathwaysQuality control pathwaysER membraneE3 complexControl pathwaysRING-type E3 ubiquitin ligasesE3 ubiquitin ligasesDominant negative mutantDoa10 substratesMisfolded proteinsUbiquitin ligasesERAD factorsMammalian cellsRING domainUBC6Substrate turnoverLuminal substratesDoa10OverexpressionPathway defectsYeastPathwayRing activityMembrane
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
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 connectionsBiochemistry. All in the ubiquitin family.
Hochstrasser M. Biochemistry. All in the ubiquitin family. Science 2000, 289: 563-4. PMID: 10939967, DOI: 10.1126/science.289.5479.563.Peer-Reviewed Original ResearchThe 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 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 functionsSubunitsSubstrate Targeting in the Ubiquitin System
Laney J, Hochstrasser M. Substrate Targeting in the Ubiquitin System. Cell 1999, 97: 427-430. PMID: 10338206, DOI: 10.1016/s0092-8674(00)80752-7.Peer-Reviewed Original ResearchA 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 conjugationEukaryotesMutantsUBLYeastInteraction 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
Degradation 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 maskingRepressorHaploidsSaccharomycesMutagenesisThere’s the Rub: a novel ubiquitin-like modification linked to cell cycle regulation
Hochstrasser M. There’s the Rub: a novel ubiquitin-like modification linked to cell cycle regulation. Genes & Development 1998, 12: 901-907. PMID: 9531529, DOI: 10.1101/gad.12.7.901.Peer-Reviewed Original Research
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 accumulationProteolysisProteinCells
1996
Autocatalytic 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
1993
The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene
Papa F, Hochstrasser M. The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene. Nature 1993, 366: 313-319. PMID: 8247125, DOI: 10.1038/366313a0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceEndopeptidasesEndosomal Sorting Complexes Required for TransportFungal ProteinsGenes, FungalHumansMiceMice, NudeMolecular Sequence DataMutationOncogene ProteinsOncogene Proteins, FusionOncogenesOpen Reading FramesPhenotypeProto-Oncogene ProteinsRecombinant Fusion ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidUbiquitin ThiolesteraseUbiquitinsMultiple ubiquitin-conjugating enzymes participate in the in vivo degradation of the yeast MATα2 repressor
Chen P, Johnson P, Sommer T, Jentsch S, Hochstrasser M. Multiple ubiquitin-conjugating enzymes participate in the in vivo degradation of the yeast MATα2 repressor. Cell 1993, 74: 357-369. PMID: 8393731, DOI: 10.1016/0092-8674(93)90426-q.Peer-Reviewed Original ResearchConceptsUbiquitin-conjugatingAttachment of ubiquitinUbiquitin-conjugating enzymeUBC proteinUbiquitination complexMolecular functionsTranscriptional regulatorsUbiquitination pathwayCellular processesSubstrate specificityDegradation signalPhysiological targetsSubstrate selectionCombinatorial mechanismsUnexpected overlapUBC6Intracellular degradationEnzymeProteinAlpha 2PathwayUbc7Deg1RepressorUbiquitin