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
Novel BET Protein Proteolysis Targeting Chimeras (BETP-PROTACs) Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma Cells
Sun B, Fiskus W, Zhang L, Raina K, Coleman K, Winkler J, Qian Y, Crew A, Shen A, Saenz D, Mill C, Wang M, Crews C, Bhalla K. Novel BET Protein Proteolysis Targeting Chimeras (BETP-PROTACs) Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma Cells. Blood 2016, 128: 1058. DOI: 10.1182/blood.v128.22.1058.1058.Peer-Reviewed Original ResearchTarget gene expressionBruton's tyrosine kinaseC-MycARV-825Transcription factorsPrimary MCL cellsTranscriptional activityGene expressionTyrosine kinaseBcl-xLE3 ubiquitin ligase activityMCL cellsUbiquitin ligase activityHuman mantle cell lymphoma cellsB-cell receptor signalingCell receptor signalingBinding of BRD4Regulation of mRNAInk4a/ArfAcetylated chromatinCopy number gainsLigase activityHematopoietic progenitor cellsBET proteinsBETi treatment
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