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
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 ResearchConceptsYeast replicative lifespanReplicative lifespanRNA-seq experimentsCoenzyme A biosynthesis pathwayYeast lifespanYeast strainsStrain librariesLifespan regulationRNA-seqGene networksDose-dependent mannerLifespan extensionTranscriptional increaseYeastLifespan measurementsWild-typeGenesMachinery componentsStrainMicrofluidic platformApplications of microfluidic platformsLifespanDeletionCoenzymePathwaySpecies-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 subunitMolecular Biology of Cytoplasmic Incompatibility Caused by Wolbachia Endosymbionts
Hochstrasser M. Molecular Biology of Cytoplasmic Incompatibility Caused by Wolbachia Endosymbionts. Annual Review Of Microbiology 2023, 77: 299-316. PMID: 37285552, DOI: 10.1146/annurev-micro-041020-024616.Peer-Reviewed Original ResearchConceptsCytoplasmic incompatibilityMale killingHost ubiquitin systemEndosymbiotic bacteriaFemale germlineEukaryotic cellsCognate partnersEmbryonic lethalityBicistronic operonUbiquitin systemDownstream genesWolbachia endosymbiontReproductive advantageCI inductionMolecular biologyInfected femalesEndosymbiontsInfections of malesReproductive alterationsDeubiquitylaseDeubiquitylasesOperonParthenogenesisArthropodsGermlineProteasomes: 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 activityEukaryotesSaccharomycesPolypeptideProteinSubstrateAssaysComplexesEctopic 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 ResearchConceptsEndoplasmic 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
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 versionInteractomeElements of the ERAD ubiquitin ligase Doa10 regulating sequential poly-ubiquitylation of its targets
Mehrtash A, Hochstrasser M. Elements of the ERAD ubiquitin ligase Doa10 regulating sequential poly-ubiquitylation of its targets. IScience 2022, 25: 105351. PMID: 36325070, PMCID: PMC9619350, DOI: 10.1016/j.isci.2022.105351.Peer-Reviewed Original ResearchC-terminal elementsUbiquitin ligase Doa10RING-CH domainDoa10 substratesSubstrate ubiquitylationRetrotranslocation channelSingle ubiquitinIntragenic suppressionCofactor-binding regionPolyubiquitin chainsDoa10E3 ubiquitinER proteinsTruncation analysisStructural predictionsStructure predictionUBC6Ubc7UbiquitylationDirect roleMechanistic insightsE2 bindsUbiquitinBindsERAD
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
2015
Site-Specific Cation Release Drives Actin Filament Severing by Vertebrate Cofilin
Kang H, Bradley M, Cao W, Zhou K, Grintsevich E, Michelot A, Reisler E, Sindelar C, Hochstrasser M, De La Cruz E. Site-Specific Cation Release Drives Actin Filament Severing by Vertebrate Cofilin. Biophysical Journal 2015, 108: 24a-25a. DOI: 10.1016/j.bpj.2014.11.159.Peer-Reviewed Original Research
2014
A second degradation signal within the short‐lived transcription factor MATalpha2 (937.1)
Hickey C, Hochstrasser M. A second degradation signal within the short‐lived transcription factor MATalpha2 (937.1). The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.937.1.Peer-Reviewed Original ResearchActin Filament Severing by Vertebrate Cofilin is Driven by Linked Cation Release
Kang H, Bradley M, McCullough B, Grintsevich E, Michelot A, Hochstrasser M, Reisler E, De La Cruz E. Actin Filament Severing by Vertebrate Cofilin is Driven by Linked Cation Release. Biophysical Journal 2014, 106: 164a-165a. DOI: 10.1016/j.bpj.2013.11.938.Peer-Reviewed Original Research
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
2010
Chapter 161 The Ubiquitin–Proteasome System
Hochstrasser M. Chapter 161 The Ubiquitin–Proteasome System. 2010, 1293-1296. DOI: 10.1016/b978-0-12-374145-5.00161-3.Peer-Reviewed Original ResearchUbiquitin-proteasome systemC-terminusMultimeric protein complexesMultiple ubiquitin moietiesFree ubiquitin poolMost DUBsUbiquitin additionUbiquitin removalUbiquitylated proteinsIndividual physiological functionsProtein complexesE1 enzymeUbiquitin moietiesUbiquitin genesUbiquitin ligationIntrinsic subunitsUbiquitin sequenceAcceptor proteinsIsopeptide bondsUbiquitin poolsUbiquitinPhysiological functionsPrecursor formDUBsIntracellular nucleophiles
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 MayerAn emerging role for thioester‐linked polyubiquitin chains in protein degradation
Ravid T, Hochstrasser M. An emerging role for thioester‐linked polyubiquitin chains in protein degradation. The FASEB Journal 2008, 22: 605.7-605.7. DOI: 10.1096/fasebj.22.1_supplement.605.7.Peer-Reviewed Original ResearchPolyubiquitin chainsE2 enzymeCatalytic cysteineUbiquitin chainsProtein quality control systemUndergoes proteasomal degradationUbiquitin chain assemblyER membraneE3 ligaseTransmembrane proteinProteasomal degradationDegradation signalProtein degradationLysine side chainsQuality control systemUbc7Lysine residuesLiving cellsChain assemblyUbiquitinCysteineEnzymeSide chainsUfd4Cue1
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