Featured Publications
The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study
Burslem GM, Smith BE, Lai AC, Jaime-Figueroa S, McQuaid DC, Bondeson DP, Toure M, Dong H, Qian Y, Wang J, Crew AP, Hines J, Crews CM. The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study. Cell Chemical Biology 2017, 25: 67-77.e3. PMID: 29129716, PMCID: PMC5831399, DOI: 10.1016/j.chembiol.2017.09.009.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesProtein familyProtein degradationTyrosine kinaseDownstream signaling responseTargeted Protein DegradationDevelopment of PROTACsTargeted degradationEndogenous proteinsSignaling responseChimera technologyCell proliferationPROTACsPROTAC technologyKinaseKinase inhibitorsLigand showAdvantages of degradationReceptor tyrosine kinase inhibitorsTyrosine kinase inhibitorsInhibitionDegradationFamilyPowerful toolProteolysis
2016
Small‐Molecule PROTACS: New Approaches to Protein Degradation
Toure M, Crews CM. Small‐Molecule PROTACS: New Approaches to Protein Degradation. Angewandte Chemie International Edition 2016, 55: 1966-1973. PMID: 26756721, DOI: 10.1002/anie.201507978.Peer-Reviewed Original ResearchConceptsProteolysis-targeting chimerasProtein degradationCellular quality control machineryQuality control machineryNovel catalytic mechanismInhibitor-based approachDrug target spaceProtein functionControl machineryProtein classesProtein destructionCatalytic mechanismCellular levelActive siteTherapeutic potentialOff-target side effectsMachineryRecent reportsChimerasDegradationRecruitmentTherapeuticsInhibition
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 interactionsInhibitorsAllosteryProteasomeSitesSubunitsInhibitionSubstrateActivityProliferationAssaysPeptidesOccupancy
2000
The Selective Proteasome Inhibitors Lactacystin and Epoxomicin Can Be Used to Either Up- or Down-Regulate Antigen Presentation at Nontoxic Doses
Schwarz K, de Giuli R, Schmidtke G, Kostka S, van den Broek M, Kim K, Crews C, Kraft R, Groettrup M. The Selective Proteasome Inhibitors Lactacystin and Epoxomicin Can Be Used to Either Up- or Down-Regulate Antigen Presentation at Nontoxic Doses. The Journal Of Immunology 2000, 164: 6147-6157. PMID: 10843664, PMCID: PMC2507740, DOI: 10.4049/jimmunol.164.12.6147.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAmino Acid SequenceAnimalsAntigen PresentationAntigens, ViralApoptosisCell DivisionCell LineCysteine EndopeptidasesCysteine Proteinase InhibitorsDose-Response Relationship, ImmunologicDown-RegulationGlycoproteinsHumansHybridomasHydrolysisLymphocyte ActivationLymphocytic choriomeningitis virusMiceMice, Inbred BALB CMice, Inbred C57BLMolecular Sequence DataMultienzyme ComplexesNucleoproteinsOligopeptidesPeptide FragmentsProteasome Endopeptidase ComplexT-Lymphocytes, CytotoxicTumor Cells, CulturedUbiquitinsUp-RegulationViral ProteinsConceptsAg presentationProteasome inhibitor lactacystinCellular proliferationProteasome activitySelective inhibitionMHC class IDose-dependent mannerTransplant rejectionAutoimmune diseasesMouse CMVAntigen presentationMost MHC class INontoxic dosesChymotrypsin-like activityClass ISelective proteasome inhibitor lactacystinApoptosis inductionMicroM lactacystinViral proteinsPresentationInhibitionComplete inhibitionLactacystinVivoProliferation
1999
Eponemycin exerts its antitumor effect through the inhibition of proteasome function.
Meng L, Kwok BH, Sin N, Crews CM. Eponemycin exerts its antitumor effect through the inhibition of proteasome function. Cancer Research 1999, 59: 2798-801. PMID: 10383134.Peer-Reviewed Original ResearchConceptsProteasome inhibitionCyclin-dependent kinase inhibitorNovel chemotherapeutic strategiesPharmacological interventionsAntitumor effectsPossible cancer therapySubunits LMP2Chemotherapeutic strategiesKinase inhibitorsCellular morphological changesCell cycle progressionCancer therapyCycle progressionInhibitionProteasome functionMorphological changesKey regulatory proteinsProteasomal subunitsTherapy
1998
The Antiproliferative Agent Didemnin B Uncompetitively Inhibits Palmitoyl Protein Thioesterase †
Meng L, Sin N, Crews C. The Antiproliferative Agent Didemnin B Uncompetitively Inhibits Palmitoyl Protein Thioesterase †. Biochemistry 1998, 37: 10488-10492. PMID: 9671519, DOI: 10.1021/bi9804479.Peer-Reviewed Original ResearchConceptsPalmitoyl-protein thioesterase 1GTP-binding proteinsDynamic protein palmitoylationDidemnin BPalmitoyl-protein thioesterasePalmitoyl proteinsProtein palmitoylationMembrane associationBaculoviral systemMyristoyl-CoAProduct bindsHa-rasBiochemical supportProteinEnzymatic activityBindingInhibition assaysDepalmitoylationPalmitoylationThioesteraseKinetic analysisInhibitionBindsRegulationUncompetitive mode