2024
Protein folding and quality control during nuclear transport
Mallik S, Poch D, Burick S, Schlieker C. Protein folding and quality control during nuclear transport. Current Opinion In Cell Biology 2024, 90: 102407. PMID: 39142062, DOI: 10.1016/j.ceb.2024.102407.Peer-Reviewed Original ResearchProtein foldingNuclear transportCo-translational transportProtein-folding environmentAggregation of folding intermediatesProtein quality controlNuclear import machineryNuclear pore complexFolding environmentImport machineryNuclear importCytosolic aggregatesContext of neurological disordersNuclear compartmentPore complexProtein synthesisProteinQuality controlFoldingBarrier functionEvolution of transport systemsKaryopherinNucleoporinsCompartmentTemporal coordination
2023
Coordinating nucleoporin condensation and nuclear pore complex assembly
Kuiper E, Prophet S, Schlieker C. Coordinating nucleoporin condensation and nuclear pore complex assembly. FEBS Letters 2023, 597: 2534-2545. PMID: 37620293, DOI: 10.1002/1873-3468.14725.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNPC assemblyNuclear pore complexNuclear pore complex assemblyPore complex assemblyAberrant condensationNPC biogenesisAssembly machineryPore complexProtein complexesComplex assemblyRepeat nucleoporinsHuman disordersAmyotrophic lateral sclerosisAssemblyEukaryotesNucleoporinsBiogenesisRibosomesRecent progressProteasomeComplexesLateral sclerosisMachineryHomeostasisTherapeutic interventions
2022
Dynamic quality control machinery that operates across compartmental borders mediates the degradation of mammalian nuclear membrane proteins
Tsai P, Cameron C, Forni M, Wasko R, Naughton B, Horsley V, Gerstein M, Schlieker C. Dynamic quality control machinery that operates across compartmental borders mediates the degradation of mammalian nuclear membrane proteins. Cell Reports 2022, 41: 111675. PMID: 36417855, PMCID: PMC9827541, DOI: 10.1016/j.celrep.2022.111675.Peer-Reviewed Original ResearchConceptsProtein turnoverCellular quality control systemNuclear membrane proteinsQuality control machineryDistinct cellular compartmentsNuclear envelope proteinsGenetic screenProtein homeostasisUbiquitin ligasesControl machineryMembrane proteinsCellular compartmentsEnzyme Ube2g2Quality control systemEndoplasmic reticulumHuman diseasesEfficient biosynthesisHRD1RNF5Disease variantsTMEM33Envelope proteinSubstrate levelsDisease etiologyModel substrateAtypical nuclear envelope condensates linked to neurological disorders reveal nucleoporin-directed chaperone activities
Prophet SM, Rampello AJ, Niescier RF, Gentile JE, Mallik S, Koleske AJ, Schlieker C. Atypical nuclear envelope condensates linked to neurological disorders reveal nucleoporin-directed chaperone activities. Nature Cell Biology 2022, 24: 1630-1641. PMID: 36302970, PMCID: PMC10041656, DOI: 10.1038/s41556-022-01001-y.Peer-Reviewed Original Researchp97/UBXD1 Generate Ubiquitylated Proteins That Are Sequestered into Nuclear Envelope Herniations in Torsin-Deficient Cells
Prophet SM, Naughton BS, Schlieker C. p97/UBXD1 Generate Ubiquitylated Proteins That Are Sequestered into Nuclear Envelope Herniations in Torsin-Deficient Cells. International Journal Of Molecular Sciences 2022, 23: 4627. PMID: 35563018, PMCID: PMC9100061, DOI: 10.3390/ijms23094627.Peer-Reviewed Original ResearchConceptsUbiquitylated proteinsNuclear pore complex assemblyPore complex assemblyNuclear envelope herniationsP97-dependent mannerP97 activityFG nucleoporinsComplex assemblyATPase deficiencyFG-NupsHeat shockHallmark phenotypeDYT1 dystoniaProteinAberrant depositionP97Therapeutic developmentDisease modelsUBXD1UbiquitylationBlebsK48UbiquitinHeterodimersUnexplored potential
2021
Nodal modulator (NOMO) is required to sustain endoplasmic reticulum morphology
Amaya C, Cameron C, Devarkar SC, Seager S, Gerstein MB, Xiong Y, Schlieker C. Nodal modulator (NOMO) is required to sustain endoplasmic reticulum morphology. Journal Of Biological Chemistry 2021, 297: 100937. PMID: 34224731, PMCID: PMC8327139, DOI: 10.1016/j.jbc.2021.100937.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumER structural integrityGenetic epistasis analysisMembrane-bound organellesP62/sequestosome 1Endoplasmic reticulum morphologyImmunoglobulin-like domainsProtein light chain 3Light chain 3Epistasis analysisIdentical orthologsProteomic screenER morphologyHuman genomeMolecular playersNOMO1Protein foldingSequestosome 1Unknown functionER networkChain 3Lipid synthesisProper functionProtein 1Orthologs
2020
Lipid and protein dynamics that shape nuclear envelope identity
Bahmanyar S, Schlieker C. Lipid and protein dynamics that shape nuclear envelope identity. Molecular Biology Of The Cell 2020, 31: 1315-1323. PMID: 32530796, PMCID: PMC7353140, DOI: 10.1091/mbc.e18-10-0636.Peer-Reviewed Original ResearchConceptsNuclear envelopeEndoplasmic reticulumMembrane fusionNuclear pore complex biogenesisUnique protein compositionBulk endoplasmic reticulumDe novo lipid synthesisNPC biogenesisComplex biogenesisNovo lipid synthesisLipid asymmetryProtein dynamicsProtein compositionElusive mechanismLipid synthesisLipid bilayersBiogenesisPermeability barrierFunctional specializationMajor threatLipid metabolismUnique compositionMitosisReticulumCompartmentalizationTorsin ATPase deficiency leads to defects in nuclear pore biogenesis and sequestration of MLF2
Rampello AJ, Laudermilch E, Vishnoi N, Prophet SM, Shao L, Zhao C, Lusk CP, Schlieker C. Torsin ATPase deficiency leads to defects in nuclear pore biogenesis and sequestration of MLF2. Journal Of Cell Biology 2020, 219: e201910185. PMID: 32342107, PMCID: PMC7265317, DOI: 10.1083/jcb.201910185.Peer-Reviewed Original ResearchConceptsNuclear pore biogenesisMyeloid leukemia factor 2FG nucleoporinsNuclear pore complex biogenesisNuclear envelope herniationsNuclear envelope reformationLive cell imaging platformProteomics-based approachNuclear envelope blebbingComplex biogenesisBleb formationUbiquitin conjugationNuclear envelopeATPase deficiencyBiogenesisHallmark phenotypePhenotypic hallmarksPOM121Factor 2Late markersLuminal componentsNup358CellsUbiquitinBlebbingThe Role of Torsin AAA+ Proteins in Preserving Nuclear Envelope Integrity and Safeguarding Against Disease
Rampello AJ, Prophet SM, Schlieker C. The Role of Torsin AAA+ Proteins in Preserving Nuclear Envelope Integrity and Safeguarding Against Disease. Biomolecules 2020, 10: 468. PMID: 32204310, PMCID: PMC7175109, DOI: 10.3390/biom10030468.Peer-Reviewed Original ResearchConceptsNuclear envelopeNuclear pore complex biogenesisEssential cellular processesNormal cellular physiologyNuclear envelope integrityDistinct subcellular localizationEndoplasmic reticulum networkCellular lipid metabolismTorsin ATPasesComplex biogenesisEnvelope integrityRegulatory cofactorsCellular physiologyCellular processesLuminal domainSubcellular localizationConsiderable medical importancePhenotypic consequencesCofactor assemblyTorsinsNE defectsATP hydrolysisReticulum networkDiverse processesPolypeptide 1
2019
An unbiased approach de-livers unexpected insight into torsin biology
Prophet SM, Schlieker C. An unbiased approach de-livers unexpected insight into torsin biology. Journal Of Clinical Investigation 2019, 129: 4576-4579. PMID: 31589164, PMCID: PMC6819095, DOI: 10.1172/jci132442.Peer-Reviewed Original ResearchConceptsFatty liver diseaseHepatic lipid metabolismLiver diseaseNonneural tissuesLipid metabolismBrain functionConditional deletionCongenital disorderDisease etiologySecretion defectHuman pathologiesMammalian liverPolypeptide 1Future investigationsSteatohepatitisUnbiased approachDysfunctionVLDLEtiologyMutationsDiseaseMiceLiverNeuronsPathologyMethodologies to monitor protein turnover at the inner nuclear membrane
Tsai PL, Zhao C, Schlieker C. Methodologies to monitor protein turnover at the inner nuclear membrane. Methods In Enzymology 2019, 619: 47-69. PMID: 30910029, PMCID: PMC6457266, DOI: 10.1016/bs.mie.2018.12.033.Peer-Reviewed Original ResearchConceptsLamin B receptorNuclear envelopeInner nuclear membrane proteinProtein turnoverProtein quality control pathwaysNuclear membrane proteinsQuality control pathwaysProtein turnover machineryHuman congenital disordersInner nuclear membraneSubcellular fractionation methodMammalian nuclear envelopeLive-cell imagingC-terminal truncationsNuclear laminaMembrane proteinsModel substrateBiochemical approachesNuclear compartmentActivity essentialControl pathwaysNuclear membraneRapid turnoverCholesterol biosynthesisCell imaging
2018
Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1: a novel mode of regulation for AAA+ ATPases
Chase A, Laudermilch E, Wang J, Shigematsu H, Yokoyama T, Schlieker C. Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1: a novel mode of regulation for AAA+ ATPases. The FASEB Journal 2018, 32: 114.1-114.1. DOI: 10.1096/fasebj.2018.32.1_supplement.114.1.Peer-Reviewed Original ResearchOligomeric stateNuclear envelope defectsRobust ATPase activityExperimental Biology 2018 MeetingPresence of ATPEnvelope defectsCofactor assemblyHomotypic oligomersCellular cofactorsATP hydrolysisDynamic assemblyFunctional assemblyMolecular etiologyATPase activationLAP1Novel modeATPase activityCofactorFASEB JournalATPasesCofactor systemATPaseAssemblyDYT1 dystoniaKey role
2017
Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1
Chase AR, Laudermilch E, Wang J, Shigematsu H, Yokoyama T, Schlieker C. Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1. Molecular Biology Of The Cell 2017, 28: 2765-2772. PMID: 28814508, PMCID: PMC5638581, DOI: 10.1091/mbc.e17-05-0281.Peer-Reviewed Original Research
2016
Dissecting Torsin/cofactor function at the nuclear envelope: a genetic study
Laudermilch E, Tsai PL, Graham M, Turner E, Zhao C, Schlieker C. Dissecting Torsin/cofactor function at the nuclear envelope: a genetic study. Molecular Biology Of The Cell 2016, 27: 3964-3971. PMID: 27798237, PMCID: PMC5156537, DOI: 10.1091/mbc.e16-07-0511.Peer-Reviewed Original ResearchConceptsTorsin ATPasesNuclear envelopeNuclear pore complex biogenesisComplex biogenesisRegulatory cofactorsValuable experimental platformHuman genomeCRISPR/Observed phenotypeGenetic studiesFunctional linkATPasesCofactor functionElectron microscopy tomographyImmunogold labelingPhenotypic measuresCell linesCofactor systemBleb structuresBleb formationTOR2ANucleoporinsLULL1BiogenesisGenomeThe Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations
Tsai PL, Zhao C, Turner E, Schlieker C. The Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations. ELife 2016, 5: e16011. PMID: 27336722, PMCID: PMC4951196, DOI: 10.7554/elife.16011.Peer-Reviewed Original ResearchConceptsLamin B receptorInner nuclear membraneNuclear membraneHuman lamin B receptorPolytopic membrane proteinsGreenberg skeletal dysplasiaProtein turnover mechanismsHigher eukaryotesDisease-causing mutationsHuman cell linesNuclear laminaMutant proteinsMembrane proteinsMutant derivativesB receptorCholesterol auxotrophyTurnover mechanismsDisease-causing variantsPoint mutationsCholesterol synthesisEnzymatic activityCofactor NADPHFunction mechanismCell linesRapid degradationSite-specific Proteolysis Mobilizes TorsinA from the Membrane of the Endoplasmic Reticulum (ER) in Response to ER Stress and B Cell Stimulation*
Zhao C, Brown RS, Tang CH, Hu CC, Schlieker C. Site-specific Proteolysis Mobilizes TorsinA from the Membrane of the Endoplasmic Reticulum (ER) in Response to ER Stress and B Cell Stimulation*. Journal Of Biological Chemistry 2016, 291: 9469-9481. PMID: 26953341, PMCID: PMC4850287, DOI: 10.1074/jbc.m115.709337.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumER stressN-terminal hydrophobic domainHydrophobic domainPrimary cellsPharmacological inhibition profileCell-permeable inhibitorProteolytic cleavage eventsMembrane-associated proteasesTorsin ATPasesATPase familyER membraneDistinct organismsGenetic manipulationCysteine residuesNuclear envelopeCleavage eventsCleavage siteOnly representativeTorsinACell linesReticulumCell stimulationProteaseCells
2015
A designed repeat protein as an affinity capture reagent.
Speltz EB, Brown RS, Hajare HS, Schlieker C, Regan L. A designed repeat protein as an affinity capture reagent. Biochemical Society Transactions 2015, 43: 874-80. PMID: 26517897, PMCID: PMC5683849, DOI: 10.1042/bst20150091.Peer-Reviewed Original ResearchConceptsProtein-peptide interactionsAffinity capture reagentsSupramolecular arraysNovel reagentCapture reagentPractical applicationsReagentsProtein engineeringGeneral utilityAffinity purificationRational fashionProtein interactionsAttractive targetInteractionImportant practical applicationsPurificationThe Torsin Activator LULL1 Is Required for Efficient Growth of Herpes Simplex Virus 1
Turner EM, Brown RS, Laudermilch E, Tsai PL, Schlieker C. The Torsin Activator LULL1 Is Required for Efficient Growth of Herpes Simplex Virus 1. Journal Of Virology 2015, 89: 8444-8452. PMID: 26041288, PMCID: PMC4524217, DOI: 10.1128/jvi.01143-15.Peer-Reviewed Original ResearchConceptsNuclear egressDouble knockout cell linesNuclear envelope dynamicsType II transmembrane proteinHerpes simplex virus 1HSV-1 nuclear egressKnockout cell linesSimplex virus 1Viral protein productionAAA ringGenome engineeringTransmembrane proteinLULL1CRISPR/Virus 1Unexpected roleProtein productionComprehensive geneticPhenotypic analysisHost cellsViral genomeEnvelope dynamicsEfficient growthCell linesHSV-1 production
2014
The mechanism of Torsin ATPase activation
Brown RS, Zhao C, Chase AR, Wang J, Schlieker C. The mechanism of Torsin ATPase activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: e4822-e4831. PMID: 25352667, PMCID: PMC4234599, DOI: 10.1073/pnas.1415271111.Peer-Reviewed Original Research
2013
Arresting a Torsin ATPase Reshapes the Endoplasmic Reticulum*
Rose AE, Zhao C, Turner EM, Steyer AM, Schlieker C. Arresting a Torsin ATPase Reshapes the Endoplasmic Reticulum*. Journal Of Biological Chemistry 2013, 289: 552-564. PMID: 24275647, PMCID: PMC3879577, DOI: 10.1074/jbc.m113.515791.Peer-Reviewed Original Research