2021
Targeted protein degradation: A promise for undruggable proteins
Samarasinghe KTG, Crews CM. Targeted protein degradation: A promise for undruggable proteins. Cell Chemical Biology 2021, 28: 934-951. PMID: 34004187, PMCID: PMC8286327, DOI: 10.1016/j.chembiol.2021.04.011.Peer-Reviewed Original ResearchConceptsProteolysis Targeting ChimerasUndruggable proteinsDisease-causing proteinsProtein degradation strategiesProteostasis mechanismsProtein homeostasisTranscription factorsProtein degradationHeterobifunctional moleculesProteinDegradation strategiesDisease initiationBiological effectsProteostasisDegradationPotential therapeutic modalityHomeostasisChimerasCellsAccumulationBET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma
Fiskus W, Mill CP, Perera D, Birdwell C, Deng Q, Yang H, Lara BH, Jain N, Burger J, Ferrajoli A, Davis JA, Saenz DT, Jin W, Coarfa C, Crews CM, Green MR, Khoury JD, Bhalla KN. BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma. Leukemia 2021, 35: 2621-2634. PMID: 33654205, PMCID: PMC8410602, DOI: 10.1038/s41375-021-01181-w.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBiomarkers, TumorBridged Bicyclo Compounds, HeterocyclicCell ProliferationCell Transformation, NeoplasticGene Expression Regulation, NeoplasticHumansLymphoma, Large B-Cell, DiffuseMicePiperidinesProteinsProteolysisSulfonamidesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsLarge B-cell lymphomaB-cell lymphomaRichter transformationBET protein inhibitorLymphoma burdenImproved survivalCombination therapyC-Myc levelsEffective therapyNovel therapiesCell lymphomaXenograft modelProtein inhibitorTherapyBET inhibitorsProtein expressionCLLGenetic alterationsLymphomaInhibitorsIRF4Single-cell RNA-seqHuman modelCRISPR knockoutCellsMajor advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs
Alabi SB, Crews C. Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs. Journal Of Biological Chemistry 2021, 296: 100647. PMID: 33839157, PMCID: PMC8131913, DOI: 10.1016/j.jbc.2021.100647.Peer-Reviewed Original ResearchConceptsProtein degradationProtein degradation pathwaysProteolysis targeting chimera (PROTAC) technologyUbiquitin-proteasome systemEndo-lysosomal pathwaySmall molecule inhibitorsDruggable spaceChemical toolsInnovative chemical toolMolecular glueChimera technologyProtein moleculesDegradation pathwayOutstanding questionsCurrent understandingMajor advancesPathwayAutophagyPROTACsDegradationCellsInhibitorsAdvances
2017
Proteolysis–Targeting Chimeras: Harnessing the Ubiquitin–Proteasome System to Induce Degradation of Specific Target Proteins
Coleman K, Crews C. Proteolysis–Targeting Chimeras: Harnessing the Ubiquitin–Proteasome System to Induce Degradation of Specific Target Proteins. Annual Review Of Cancer Biology 2017, 2: 1-18. DOI: 10.1146/annurev-cancerbio-030617-050430.Peer-Reviewed Original ResearchProteolysis-targeting chimerasSpecific target proteinsUbiquitin-proteasome systemTarget proteinsNew cell biologyCancer Biology Volume 2Accumulation of proteinsProtein homeostasisUndruggable proteinsE3 ubiquitinMammalian cellsCell biologyProteasome complexFinal online publication dateProteinOnline publication dateProteolytic degradationMultistep processCancer cellsProteasome inhibitorsPathological proteinsNovel therapeuticsCentral roleBifunctional moleculesCells
2015
Specific Induction of Golgi Stress by Targeted Protein Destabilization
Serebrenik Y, Crews C. Specific Induction of Golgi Stress by Targeted Protein Destabilization. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.723.5.Peer-Reviewed Original Research