Featured Publications
Catalytic in vivo protein knockdown by small-molecule PROTACs
Bondeson DP, Mares A, Smith IE, Ko E, Campos S, Miah AH, Mulholland KE, Routly N, Buckley DL, Gustafson JL, Zinn N, Grandi P, Shimamura S, Bergamini G, Faelth-Savitski M, Bantscheff M, Cox C, Gordon DA, Willard RR, Flanagan JJ, Casillas LN, Votta BJ, den Besten W, Famm K, Kruidenier L, Carter PS, Harling JD, Churcher I, Crews CM. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nature Chemical Biology 2015, 11: 611-617. PMID: 26075522, PMCID: PMC4629852, DOI: 10.1038/nchembio.1858.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBinding SitesBiocatalysisBreast NeoplasmsFemaleHumansMCF-7 CellsMiceModels, MolecularMolecular Targeted TherapyNeoplasm ProteinsNeoplasm TransplantationProteasome Endopeptidase ComplexProtein BindingProteolysisReceptor-Interacting Protein Serine-Threonine Kinase 2Receptors, EstrogenSmall Molecule LibrariesUbiquitinUbiquitinationVon Hippel-Lindau Tumor Suppressor ProteinChemical 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
2001
Protacs: Chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation
Sakamoto K, Kim K, Kumagai A, Mercurio F, Crews C, Deshaies R. Protacs: Chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 8554-8559. PMID: 11438690, PMCID: PMC37474, DOI: 10.1073/pnas.141230798.Peer-Reviewed Original ResearchConceptsSkp1-CullinF-box complexAttachment of ubiquitinUbiquitin-dependent proteolysisMetAP-2Disease-causing proteinsMethionine aminopeptidase 2SCF complexBeta-TRCPConditional inactivationBox complexChimeric moleculesProteinUbiquitinationIntracellular levelsUbiquitinChimeric compoundsAngiogenesis inhibitorsHRT1ComplexesPhosphopeptidesDomainProteolysisEnzymeDegradation