2014
Small‐Molecule Control of Intracellular Protein Levels through Modulation of the Ubiquitin Proteasome System
Buckley DL, Crews CM. Small‐Molecule Control of Intracellular Protein Levels through Modulation of the Ubiquitin Proteasome System. Angewandte Chemie International Edition 2014, 53: 2312-2330. PMID: 24459094, PMCID: PMC4348030, DOI: 10.1002/anie.201307761.Peer-Reviewed Original ResearchConceptsSmall molecule modulatorsProtein levelsSmall-molecule probesUbiquitin-proteasome systemActivity of proteinsIntracellular protein levelsBiological probesProteasome systemProtein degradationUbiquitin-proteasomeProtein activitySmall moleculesMolecule controlDruggable targetsProteomeProteasomeTargeted fashionProteinRemaining majorityGlobal increaseProbeUPSMoleculesDegradationMultiple strategies
2008
ChemInform Abstract: Chemical Genetics: Exploring the Role of the Proteasome in Cell Biology Using Natural Products and Other Small Molecule Proteasome Inhibitors
Kim K, Crews C. ChemInform Abstract: Chemical Genetics: Exploring the Role of the Proteasome in Cell Biology Using Natural Products and Other Small Molecule Proteasome Inhibitors. ChemInform 2008, 39: no-no. DOI: 10.1002/chin.200829270.Peer-Reviewed Original Research
2003
Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro
Garrett IR, Chen D, Gutierrez G, Zhao M, Escobedo A, Rossini G, Harris SE, Gallwitz W, Kim KB, Hu S, Crews CM, Mundy GR. Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. Journal Of Clinical Investigation 2003, 111: 1771-1782. PMID: 12782679, PMCID: PMC156102, DOI: 10.1172/jci16198.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, NorthernBlotting, WesternBone and BonesBone DevelopmentBone Morphogenetic Protein 2Bone Morphogenetic Protein 4Bone Morphogenetic ProteinsCarrier ProteinsCell DivisionCell LineCysteine EndopeptidasesDNADose-Response Relationship, DrugEnzyme-Linked Immunosorbent AssayGenetic VectorsHumansLuciferasesMiceMice, Inbred ICRMultienzyme ComplexesOrgan Culture TechniquesOsteoblastsPromoter Regions, GeneticProteasome Endopeptidase ComplexProteinsRNA, MessengerSkullTranscription, GeneticTransfectionTransforming Growth Factor betaConceptsUbiquitin-proteasome pathwayBMP-4BMP-2Osteoblast differentiationBMP-6 mRNA expressionUbiquitin-proteasome machineryEffect of nogginCatalytic beta subunitsProteasome inhibitorsBMP-2 gene expressionBone morphogenetic protein-2Drosophila homologueMorphogenetic protein-2Gli3 proteinGene expressionBeta subunitProteolytic processingProtein 2Bone formationDifferent inhibitorsEndogenous inhibitorOsteoblastic cellsProteasomeNogginInhibitor-1
2001
The ubiquitin‐proteasome pathway and proteasome inhibitors
Myung J, Kim K, Crews C. The ubiquitin‐proteasome pathway and proteasome inhibitors. Medicinal Research Reviews 2001, 21: 245-273. PMID: 11410931, PMCID: PMC2556558, DOI: 10.1002/med.1009.Peer-Reviewed Original ResearchConceptsUbiquitin-proteasome pathwayComplex biochemical machineryHuman diseasesDiverse cellular processesImportant cellular substratesMajor cellular networksCellular processesBiochemical machineryProtein degradationNatural proteasome inhibitorsCellular substratesCentral playerIntracellular processesMode of actionProteasome inhibitorsPathwayMolecular probesInhibitorsPotential therapeutic agentProteasomeImportant componentMachineryRegulationTherapeutic agentsLack of Proteasome Active Site Allostery as Revealed by Subunit-Specific Inhibitors
Myung J, Kim K, Lindsten K, Dantuma N, Crews C. Lack of Proteasome Active Site Allostery as Revealed by Subunit-Specific Inhibitors. Molecular Cell 2001, 7: 411-420. PMID: 11239469, DOI: 10.1016/s1097-2765(01)00188-5.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsBinding SitesCattleCell DivisionCells, CulturedChymotrypsinCysteine EndopeptidasesEndopeptidasesEpoxy CompoundsHumansHydrolysisKetonesKineticsModels, BiologicalMultienzyme ComplexesProtease InhibitorsProteasome Endopeptidase ComplexProtein SubunitsRecombinant Fusion ProteinsSerineSubstrate SpecificityTransfectionConceptsProtein degradation assaysSubunit-specific inhibitorsProtein degradationDegradation assaysCellular proliferationChymotrypsin-like activityPeptidyl-glutamyl peptideEpoxyketone inhibitorsActive siteSuch interactionsInhibitorsAllosteryProteasomeSitesSubunitsInhibitionSubstrateActivityProliferationAssaysPeptidesOccupancyCells adapted to the proteasome inhibitor 4-hydroxy- 5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival
Princiotta M, Schubert U, Chen W, Bennink J, Myung J, Crews C, Yewdell J. Cells adapted to the proteasome inhibitor 4-hydroxy- 5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 513-518. PMID: 11149939, PMCID: PMC14618, DOI: 10.1073/pnas.98.2.513.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Chloromethyl KetonesAminopeptidasesAnimalsAntigen PresentationAntigensBoronic AcidsBortezomibCD8-Positive T-LymphocytesCell SurvivalCysteine EndopeptidasesDipeptidyl-Peptidases and Tripeptidyl-PeptidasesDrug ResistanceEndopeptidasesEnzyme ActivationH-2 AntigensLeupeptinsLymphoma, T-CellMiceMultienzyme ComplexesNeoplasm ProteinsOligopeptidesPeptide FragmentsPhenolsProtease InhibitorsProteasome Endopeptidase ComplexProtein Processing, Post-TranslationalPyrazinesSelection, GeneticSerine EndopeptidasesSulfonesThymus NeoplasmsTumor Cells, CulturedTumor Suppressor Protein p53TyramineUbiquitinsConceptsII activityLarge proteolytic complexSpecific proteasome inhibitorInhibitor 4Degradation of p53Ala-AlaProteolytic complexPolyubiquitinated proteinsLeu-LeuProteolytic functionActive proteasomesPrimary proteaseProperties of cellsProteolytic systemProteasomeSpecific inhibitorMajor histocompatibility complexPhe-chloromethylketoneProteasome inhibitors