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 substratep97/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
2020
Torsin 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 componentsNup358CellsUbiquitinBlebbing
2011
Enzymatic Blockade of the Ubiquitin-Proteasome Pathway
Ernst R, Claessen JH, Mueller B, Sanyal S, Spooner E, van der Veen AG, Kirak O, Schlieker CD, Weihofen WA, Ploegh HL. Enzymatic Blockade of the Ubiquitin-Proteasome Pathway. PLOS Biology 2011, 8: e1000605. PMID: 21468303, PMCID: PMC3066133, DOI: 10.1371/journal.pbio.1000605.Peer-Reviewed Original Research
2009
The Otubain YOD1 Is a Deubiquitinating Enzyme that Associates with p97 to Facilitate Protein Dislocation from the ER
Ernst R, Mueller B, Ploegh HL, Schlieker C. The Otubain YOD1 Is a Deubiquitinating Enzyme that Associates with p97 to Facilitate Protein Dislocation from the ER. Molecular Cell 2009, 36: 28-38. PMID: 19818707, PMCID: PMC2774717, DOI: 10.1016/j.molcel.2009.09.016.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAlpha 1-AntitrypsinCarrier ProteinsCatalytic DomainCell Cycle ProteinsCell LineEndopeptidasesEndoplasmic ReticulumHumansMembrane ProteinsPoint MutationProteasome Endopeptidase ComplexProtein BindingProtein FoldingProtein Interaction Domains and MotifsProtein TransportReceptors, Antigen, T-Cell, alpha-betaThiolester HydrolasesTransfectionUbiquitinUbiquitinationValosin Containing ProteinZinc FingersConceptsZinc finger domainOvarian tumor (OTU) familyDominant negative effectMisfolded proteinsMultiprotein complexesFinger domainMammalian cellsDislocation substratesProtein dislocationC-terminusEndoplasmic reticulumFunctional linkYOD1P97Core domainEnzymeUbxTumor familyTerminusCytosolDomainProteinReticulumPathwayRole
2007
Structure of a Herpesvirus-Encoded Cysteine Protease Reveals a Unique Class of Deubiquitinating Enzymes
Schlieker C, Weihofen WA, Frijns E, Kattenhorn LM, Gaudet R, Ploegh HL. Structure of a Herpesvirus-Encoded Cysteine Protease Reveals a Unique Class of Deubiquitinating Enzymes. Molecular Cell 2007, 25: 677-687. PMID: 17349955, PMCID: PMC7110467, DOI: 10.1016/j.molcel.2007.01.033.Peer-Reviewed Original ResearchConceptsDeubiquitinating enzymePapain-like foldCysteine protease domainLarge tegument proteinActive site cysteineActive site residuesBeta-hairpin loopExtensive hydrophobic interactionsSuicide substrateProtease moduleProtease domainTegument proteinsCysteine proteasesHairpin loopEnzymeThioether linkageUbUnique classHydrophobic interactionsMurine cytomegalovirusUbiquitinDomainProteinMembersCrystal structure