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
2015
HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins
Buckley DL, Raina K, Darricarrere N, Hines J, Gustafson JL, Smith IE, Miah AH, Harling JD, Crews CM. HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins. ACS Chemical Biology 2015, 10: 1831-1837. PMID: 26070106, PMCID: PMC4629848, DOI: 10.1021/acschembio.5b00442.Peer-Reviewed Original ResearchConceptsChemical probesMore drug-like propertiesFusion proteinSmall-molecule PROTACsProtein degradationDrug-like propertiesE3 ligase ligandChemical genetic toolsSpecific E3 ligasesProtein of interestVHL ligandsHaloTag fusion proteinsE3 ligasesGenetic toolsHeterobifunctional moleculesNumerous proteinsHaloPROTACLigandsPROTACsProteinNovel classAttractive strategyDegradationProbeLigases
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
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