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 toolProteolysisChemical Genetic Control of Protein Levels: Selective in Vivo Targeted Degradation
Schneekloth JS, Fonseca FN, Koldobskiy M, Mandal A, Deshaies R, Sakamoto K, Crews CM. Chemical Genetic Control of Protein Levels: Selective in Vivo Targeted Degradation. Journal Of The American Chemical Society 2004, 126: 3748-3754. PMID: 15038727, DOI: 10.1021/ja039025z.Peer-Reviewed Original ResearchConceptsGreen fluorescent proteinProtein functionCell biological questionsGenetic model systemUbiquitin-proteasome pathwayChemical knockoutTargeted degradationBiological questionsProtein degradationGenetic strategiesGenetic controlGenetic lossTarget proteinsFluorescent proteinChimeric moleculesCultured cellsFKBP12 ligandsProteinProtein levelsModel systemWestern blotGeneral strategyFunction analysisVivo examplesFluorometric analysis
2021
Targeted degradation of transcription factors by TRAFTACs: TRAnscription Factor TArgeting Chimeras
Samarasinghe KTG, Jaime-Figueroa S, Burgess M, Nalawansha DA, Dai K, Hu Z, Bebenek A, Holley SA, Crews CM. Targeted degradation of transcription factors by TRAFTACs: TRAnscription Factor TArgeting Chimeras. Cell Chemical Biology 2021, 28: 648-661.e5. PMID: 33836141, PMCID: PMC8524358, DOI: 10.1016/j.chembiol.2021.03.011.Peer-Reviewed Original ResearchConceptsTranscription factorsTargeted degradationTranscription factor degradationDNA-binding proteinsMultiple signaling pathwaysGeneralizable strategyDCas9 proteinProtein familyLigandable sitesProteasomal pathwaySignaling pathwaysOverexpression of oncoproteinsAberrant activationChimeric oligonucleotideProteinChimerasFactor degradationNF-κBPathwayHaloTagDegradationBrachyuryOverexpressionOncoproteinOligonucleotide
2020
Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs
Bond MJ, Chu L, Nalawansha DA, Li K, Crews CM. Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs. ACS Central Science 2020, 6: 1367-1375. PMID: 32875077, PMCID: PMC7453568, DOI: 10.1021/acscentsci.0c00411.Peer-Reviewed Original Research