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 ResearchMeSH KeywordsAnimalsBinding SitesCells, CulturedDNA-Binding ProteinsHEK293 CellsHumansOligonucleotidesTranscription FactorsZebrafishConceptsTranscription factorsTargeted degradationTranscription factor degradationDNA-binding proteinsMultiple signaling pathwaysGeneralizable strategyDCas9 proteinProtein familyLigandable sitesProteasomal pathwaySignaling pathwaysOverexpression of oncoproteinsAberrant activationChimeric oligonucleotideProteinChimerasFactor degradationNF-κBPathwayHaloTagDegradationBrachyuryOverexpressionOncoproteinOligonucleotide
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
2001
Lack of Proteasome Active Site Allostery as Revealed by Subunit-Specific Inhibitors
Myung J, Kim K, Lindsten K, Dantuma N, Crews C. Lack of Proteasome Active Site Allostery as Revealed by Subunit-Specific Inhibitors. Molecular Cell 2001, 7: 411-420. PMID: 11239469, DOI: 10.1016/s1097-2765(01)00188-5.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsBinding SitesCattleCell DivisionCells, CulturedChymotrypsinCysteine EndopeptidasesEndopeptidasesEpoxy CompoundsHumansHydrolysisKetonesKineticsModels, BiologicalMultienzyme ComplexesProtease InhibitorsProteasome Endopeptidase ComplexProtein SubunitsRecombinant Fusion ProteinsSerineSubstrate SpecificityTransfectionConceptsProtein degradation assaysSubunit-specific inhibitorsProtein degradationDegradation assaysCellular proliferationChymotrypsin-like activityPeptidyl-glutamyl peptideEpoxyketone inhibitorsActive siteSuch interactionsInhibitorsAllosteryProteasomeSitesSubunitsInhibitionSubstrateActivityProliferationAssaysPeptidesOccupancy
2000
The antiangiogenic agent TNP-470 requires p53 and p21CIP/WAF for endothelial cell growth arrest
Yeh J, Mohan R, Crews C. The antiangiogenic agent TNP-470 requires p53 and p21CIP/WAF for endothelial cell growth arrest. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 12782-12787. PMID: 11070090, PMCID: PMC18841, DOI: 10.1073/pnas.97.23.12782.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiogenesis InhibitorsAnimalsCell CycleCell DivisionCells, CulturedCorneal NeovascularizationCyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsCyclohexanesEndothelium, VascularGene ExpressionHumansMiceMice, KnockoutNuclear ProteinsO-(Chloroacetylcarbamoyl)fumagillolProto-Oncogene ProteinsProto-Oncogene Proteins c-mdm2SesquiterpenesTumor Suppressor Protein p53ConceptsTNP-470Endothelial cellsAntiangiogenic agent TNP-470Subsequent growth arrestGrowth arrestCyclin-dependent kinase inhibitorAntiangiogenic strategiesPrimary endothelial cellsEndothelial cell growth arrestP21CIP/WAFEndothelial cell cycleCell growth arrestKinase inhibitorsAntiangiogenic activityCell cycle regulatorsAngiogenesis assayCytostatic activityP53 activationMiceCritical cell cycle regulatorsCycle regulatorsUnique mechanismAdult fibroblastsCell-type specificityArrest
1999
Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide α', β'-epoxyketones
Elofsson M, Splittgerber U, Myung J, Mohan R, Crews C. Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide α', β'-epoxyketones. Cell Chemical Biology 1999, 6: 811-822. PMID: 10574782, DOI: 10.1016/s1074-5521(99)80128-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaCattleCell DivisionCells, CulturedChymotrypsinCysteine EndopeptidasesCysteine Proteinase InhibitorsDrug DesignEndothelium, VascularEpoxy CompoundsGlutamatesIndicators and ReagentsIrritantsKineticsMacromolecular SubstancesMiceMolecular ConformationMultienzyme ComplexesPeptidesProteasome Endopeptidase ComplexTrypsinConceptsCatalytic activityMolecular probesAcetylated peptidesExcellent selectivityPotent proteasome inhibitorVivo anti-inflammatory activityMost compoundsMajor catalytic activityChymotrypsin-like activityPeptide αAromatic amino acidsEpoxyketonesAminoP2-P4Multicatalytic protease complexPeptidesAnti-inflammatory activitySelectivityProbeLarge multicatalytic protease complexesProteasome inhibitorsAmino acidsSynthesisCompoundsComplexesEpoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity
Meng L, Mohan R, Kwok B, Elofsson M, Sin N, Crews C. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 10403-10408. PMID: 10468620, PMCID: PMC17900, DOI: 10.1073/pnas.96.18.10403.Peer-Reviewed Original ResearchAnimalsAntibiotics, AntineoplasticAnti-Inflammatory Agents, Non-SteroidalCattleCells, CulturedCysteine EndopeptidasesCysteine Proteinase InhibitorsEndothelium, VascularErythrocytesHeLa CellsHumansKineticsMultienzyme ComplexesOligopeptidesProteasome Endopeptidase ComplexTumor Cells, CulturedTumor Suppressor Protein p53UbiquitinsUmbilical VeinsEponemycin exerts its antitumor effect through the inhibition of proteasome function.
Meng L, Kwok BH, Sin N, Crews CM. Eponemycin exerts its antitumor effect through the inhibition of proteasome function. Cancer Research 1999, 59: 2798-801. PMID: 10383134.Peer-Reviewed Original ResearchConceptsProteasome inhibitionCyclin-dependent kinase inhibitorNovel chemotherapeutic strategiesPharmacological interventionsAntitumor effectsPossible cancer therapySubunits LMP2Chemotherapeutic strategiesKinase inhibitorsCellular morphological changesCell cycle progressionCancer therapyCycle progressionInhibitionProteasome functionMorphological changesKey regulatory proteinsProteasomal subunitsTherapy
1998
Eponemycin analogues: syntheses and use as probes of angiogenesis
Sin N, Meng L, Auth H, Crews C. Eponemycin analogues: syntheses and use as probes of angiogenesis. Bioorganic & Medicinal Chemistry 1998, 6: 1209-1217. PMID: 9784862, DOI: 10.1016/s0968-0896(98)00089-3.Peer-Reviewed Original Research
1992
Phorbol ester stimulates a protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product.
Alessandrini A, Crews CM, Erikson RL. Phorbol ester stimulates a protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 8200-8204. PMID: 1518847, PMCID: PMC49885, DOI: 10.1073/pnas.89.17.8200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCells, CulturedIn Vitro TechniquesMiceMitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesMolecular Sequence DataMutagenesis, Site-DirectedOligodeoxyribonucleotidesPeptide MappingPhorbol EstersPhosphorylationPhosphothreonineProtein KinasesProtein-Tyrosine KinasesT-LymphocytesConceptsProtein kinase activityProtein kinaseGene productsKinase activityMyelin basic protein kinaseMyelin basic protein kinase activityMultiple extracellular signalsUpstream protein kinaseWild-type proteinIdentification of proteinsAmino acid residuesSame amino acid residuesERK-1 proteinDegree of phosphorylationReversible phosphorylationThreonine sitesThreonine kinaseExtracellular signalsTyrosine sitesAcid residuesKinasePhosphorylationPhorbol esterProteinThreonine