2022
PROTACs: past, present and future
Li K, Crews CM. PROTACs: past, present and future. Chemical Society Reviews 2022, 51: 5214-5236. PMID: 35671157, PMCID: PMC10237031, DOI: 10.1039/d2cs00193d.Peer-Reviewed Original ResearchConceptsProtein of interestProteolysis-targeting chimerasUbiquitin-proteasome systemE3 ubiquitin ligaseSmall molecule inhibitorsUbiquitin ligaseNonenzymatic functionProtein degradationHeterobifunctional moleculesDrug resistance mechanismsMolecule inhibitorsSubsequent degradationUbiquitinationLigasePromising therapeuticsProteinChimerasPotential toxicityDegradationMechanism
2013
A Bidirectional System for the Dynamic Small Molecule Control of Intracellular Fusion Proteins
Neklesa TK, Noblin DJ, Kuzin A, Lew S, Seetharaman J, Acton TB, Kornhaber G, Xiao R, Montelione G, Tong L, Crews CM. A Bidirectional System for the Dynamic Small Molecule Control of Intracellular Fusion Proteins. ACS Chemical Biology 2013, 8: 2293-2300. PMID: 23978068, PMCID: PMC4113957, DOI: 10.1021/cb400569k.Peer-Reviewed Original ResearchConceptsSmall molecule controlProtein functionFusion proteinMolecule controlIntracellular fusion proteinOncogenic H-RasCellular protein levelsProtein of interestProtein levelsSmall-molecule screenIntracellular protein levelsDose-dependent regulationCellular transformationH-RasMolecule screenPhysiological roleProteinTherapeutic targetDose-dependent mannerHydrophobic tagUbiquitinationBidirectional controlHSP70DehalogenaseRegulation
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