2024
EGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling
Hu Z, Chen P, Li W, Krone M, Zheng S, Saarbach J, Velasco I, Hines J, Liu Y, Crews C. EGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling. Science Advances 2024, 10: eadj7251. PMID: 38536914, PMCID: PMC10971414, DOI: 10.1126/sciadv.adj7251.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell Line, TumorErbB ReceptorsHumansPhosphorylationProteolysis Targeting ChimeraSignal TransductionTyrosineConceptsInhibit cancer cell viabilityProteome-wide levelCancer cell viabilityDifferential signaling pathwaysPhosphoproteomic approachTyrosine dephosphorylationProtein dephosphorylationSignal transductionActivating dephosphorylationInduce apoptosisReceptor tyrosine kinase inhibitorsRTK activationSignaling pathwayInhibition of kinasesDephosphorylationEpidermal growth factor receptorGrowth factor receptorCell viabilityFactor receptorInhibitory approachesTyrosineTyrosine kinase inhibitorsInhibitory effectInhibitory potentialKinase inhibitors
2017
BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells
Sun B, Fiskus W, Qian Y, Rajapakshe K, Raina K, Coleman KG, Crew AP, Shen A, Saenz DT, Mill CP, Nowak AJ, Jain N, Zhang L, Wang M, Khoury JD, Coarfa C, Crews CM, Bhalla KN. BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells. Leukemia 2017, 32: 343-352. PMID: 28663582, DOI: 10.1038/leu.2017.207.Peer-Reviewed Original ResearchConceptsMantle cell lymphoma cellsMCL cellsCell lymphoma cellsARV-825ARV-771Lymphoma cellsGreater survival improvementSuperior preclinical activityCDK4/6 inhibitor palbociclibNuclear factor-κB (NF-κB) target genesExtraterminal protein inhibitorSurvival improvementInhibitor palbociclibPreclinical activityCDKN1A/p21Inhibitor treatmentSuperior pharmacological propertiesVivo growthCyclin D1Pharmacological propertiesProtein expressionMore apoptosisVivo evaluationIncomplete inhibitionC-Myc
2015
Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4
Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, Hines J, Winkler JD, Crew AP, Coleman K, Crews CM. Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. Cell Chemical Biology 2015, 22: 755-763. PMID: 26051217, PMCID: PMC4475452, DOI: 10.1016/j.chembiol.2015.05.009.Peer-Reviewed Original ResearchAcetanilidesAdaptor Proteins, Signal TransducingApoptosisAzepinesCell Cycle ProteinsCell Line, TumorCell ProliferationHeterocyclic Compounds, 3-RingHumansNuclear ProteinsPeptide HydrolasesProto-Oncogene Proteins c-mycSignal TransductionThalidomideTranscription FactorsTriazolesUbiquitin-Protein Ligases
2014
Targeted protein destabilization reveals an estrogen-mediated ER stress response
Raina K, Noblin DJ, Serebrenik YV, Adams A, Zhao C, Crews CM. Targeted protein destabilization reveals an estrogen-mediated ER stress response. Nature Chemical Biology 2014, 10: 957-962. PMID: 25242550, PMCID: PMC4324732, DOI: 10.1038/nchembio.1638.Peer-Reviewed Original Research
2013
Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs
Hines J, Gough JD, Corson TW, Crews CM. Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 8942-8947. PMID: 23674677, PMCID: PMC3670320, DOI: 10.1073/pnas.1217206110.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnalysis of VarianceAnimalsChromatography, High Pressure LiquidEnzyme ActivationFemaleGene Knockdown TechniquesHumansImmunoblottingMCF-7 CellsMiceMolecular Sequence DataMolecular StructurePC12 CellsPhosphatidylinositol 3-KinasesPhosphorylationProtein Processing, Post-TranslationalProteolysisRatsReceptor Protein-Tyrosine KinasesReceptor, ErbB-3Receptor, Fibroblast Growth Factor, Type 2Receptor, trkASignal TransductionStreptavidinVon Hippel-Lindau Tumor Suppressor ProteinConceptsGrowth factor receptorProtein knockdownFibroblast growth factor receptor substrateVon Hippel-Lindau proteinSpecific receptor tyrosine kinasesKinase-mediated phosphorylationReceptor tyrosine kinase pathwaysFactor receptorKinase signal pathwayTyrosine kinase activationReceptor tyrosine kinasesTyrosine kinase pathwayConditional degradationPhosphorylation sequenceKinase pathwayReceptor substrateKinase activationNucleic acid-based strategiesLindau proteinTarget protein knockdownSpecific proteinsTyrosine kinaseCell-type selectivityNerve growth factor receptorKnockdown
2006
Probing Protein Function with Small Molecules
Gough JD, Crews CM. Probing Protein Function with Small Molecules. Ernst Schering Foundation Symposium Proceedings 2006, 58: 61-74. PMID: 16708999, DOI: 10.1007/978-3-540-37635-4_5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiotinylationCombinatorial Chemistry TechniquesDrug DesignDrug Evaluation, PreclinicalGenomicsGreen Fluorescent ProteinsHumansKetonesModels, ChemicalMolecular Probe TechniquesNanotechnologyOligopeptidesPhosphorylationProtein BindingProteinsReceptors, AndrogenRecombinant Fusion ProteinsSerineSesquiterpenesSignal TransductionUbiquitin-Protein Ligases
1996
Deciphering isozyme function: exploring cell biology with chemistry in the post-genomic era
Crews C. Deciphering isozyme function: exploring cell biology with chemistry in the post-genomic era. Cell Chemical Biology 1996, 3: 961-965. PMID: 9000005, DOI: 10.1016/s1074-5521(96)90162-3.Peer-Reviewed Original Research
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 phosphorylationExtracellular signals and reversible protein phosphorylation: What to Mek of it all
Crews C, Erikson R. Extracellular signals and reversible protein phosphorylation: What to Mek of it all. Cell 1993, 74: 215-217. PMID: 8343948, DOI: 10.1016/0092-8674(93)90411-i.Peer-Reviewed Original Research