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
Lack 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 interactionsInhibitorsAllosteryProteasomeSitesSubunitsInhibitionSubstrateActivityProliferationAssaysPeptidesOccupancyThe anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IκB kinase
Kwok B, Koh B, Ndubuisi M, Elofsson M, Crews C. The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IκB kinase. Cell Chemical Biology 2001, 8: 759-766. PMID: 11514225, DOI: 10.1016/s1074-5521(01)00049-7.Peer-Reviewed Original ResearchConceptsAnti-inflammatory activityHerb feverfewPro-inflammatory signaling pathwaysDirect molecular targetVivo anti-inflammatory activityAnti-inflammatory propertiesAnti-inflammatory agentsCytokine-mediated stimulationCytokine-mediated signalingIkappaB kinase betaSesquiterpene lactone parthenolidePharmaceutical interventionsIκB kinaseMolecular targetsNatural product parthenolideKinase betaParthenolideCysteine 179Signaling pathwaysPossible molecular basisIntracellular signaling processesAttractive targetIKK complexMolecular mechanismsAlpha-methylene gamma-lactone moiety
1993
Reconstitution of the Raf-1-MEK-ERK signal transduction pathway in vitro.
Macdonald SG, Crews CM, Wu L, Driller J, Clark R, Erikson RL, McCormick F. Reconstitution of the Raf-1-MEK-ERK signal transduction pathway in vitro. Molecular And Cellular Biology 1993, 13: 6615-6620. PMID: 8413257, PMCID: PMC364724, DOI: 10.1128/mcb.13.11.6615.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBaculoviridaeCell LineCloning, MolecularGenes, rasGenes, srcHumansMAP Kinase Kinase 1Mitogen-Activated Protein Kinase KinasesMothsMutagenesis, Site-DirectedPhosphorylationPolymerase Chain ReactionProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-rafProto-Oncogene Proteins p21(ras)Recombinant ProteinsSignal TransductionTransfectionConceptsRaf-1V-SrcV-rasSf9 cellsGlutathione S-transferase fusion proteinS-transferase fusion proteinSerine/threonine kinaseProtein kinase C phosphorylationKinase-inactive versionERK signal transduction pathwayKinase-inactive mutantRaf-1 phosphorylationKinase C phosphorylationSignal transduction pathwaysRaf-1-MEKActivation of MEKTyrosine kinase oncogenesProtein kinase CAutokinase activityFunction upstreamThreonine kinaseDirect substrateMEK activationTransduction pathwaysC phosphorylation