2020
EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair
Koyen A, Madden M, Park D, Minten E, Kapoor-Vazirani P, Werner E, Pfister N, Haji-Seyed-Javadi R, Zhang H, Xu J, Deng N, Duong D, Pecen T, Frazier Z, Nagel Z, Lazaro J, Mouw K, Seyfried N, Moreno C, Owonikoko T, Deng X, Yu D. EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair. Oncogene 2020, 39: 4798-4813. PMID: 32457468, PMCID: PMC7305988, DOI: 10.1038/s41388-020-1332-2.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerCisplatin resistanceSCLC cellsCisplatin-based chemotherapyCell lung cancerImportant therapeutic targetZeste homolog 2Cellular cisplatinPoor outcomeAggressive malignancyNucleotide excision repairLung cancerClinical investigationTherapeutic targetEZH2 depletionPolycomb repressive complex 2Homolog 2DDB1-DDB2EZH2Important regulatorRepairExcision repairMethyltransferase activityPRC2-independent functionSynthetic lethality screen
2019
Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression
Tsankov AM, Wadsworth MH, Akopian V, Charlton J, Allon SJ, Arczewska A, Mead BE, Drake RS, Smith ZD, Mikkelsen TS, Shalek AK, Meissner A. Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression. Development 2019, 146: dev174722. PMID: 31515224, PMCID: PMC6803377, DOI: 10.1242/dev.174722.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleCell DifferentiationDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEnhancer Elements, GeneticEntropyGene Expression Regulation, DevelopmentalHuman Embryonic Stem CellsHumansMaleRepressor ProteinsRNA, MessengerTranscription, GeneticConceptsGlobal methylation levelsTranscriptional repressionSingle-cell RNA-sequencing dataMethylation levelsNew cell fatesMaintenance of pluripotencyHuman embryonic stem cellsMethylation of cytosineRNA-sequencing dataCell-cell variabilityStem cellsEmbryonic stem cellsHuman pluripotent stem cellsDNA methyltransferase activityMRNA expression dataPluripotent stem cellsTranscriptional variabilityMethyltransferases Dnmt3aCell fateEpigenetic regulatorsMethyltransferase DNMT3AExtrinsic signalsHigh-resolution viewMethyltransferase activityProper differentiation
2017
SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth
Tamiya H, Kim H, Klymenko O, Kim H, Feng Y, Zhang T, Han JY, Murao A, Snipas SJ, Jilaveanu L, Brown K, Kluger H, Zhang H, Iwai K, Ronai Z. SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth. Journal Of Clinical Investigation 2017, 128: 517-530. PMID: 29227283, PMCID: PMC5749505, DOI: 10.1172/jci95410.Peer-Reviewed Original ResearchConceptsLinear ubiquitin chain assembly complexType II protein arginine methyltransferaseProtein arginine methyltransferase 5Protein arginine methyltransferaseTranscription factor Sox10Cyclin-dependent kinase inhibitor 2ATranscriptional corepressor SKIArginine dimethylationArginine methyltransferasePRMT5 activityAssembly complexMelanoma growthMethyltransferase activityPRMT5PRMT5 inhibitionRegulatory axisInhibitor 2ASHARPINNF-κB signalingHuman cancersMethylthioadenosine phosphorylaseMultiproteinImportant roleDimethylationMethyltransferase
2016
Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus
Li N, Subrahmanyan L, Smith E, Yu X, Zaidi S, Choi M, Mane S, Nelson-Williams C, Behjati M, Kazemi M, Hashemi M, Fathzadeh M, Narayanan A, Tian L, Montazeri F, Mani M, Begleiter ML, Coon BG, Lynch HT, Olson EN, Zhao H, Ruland J, Lifton RP, Mani A. Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus. American Journal Of Human Genetics 2016, 98: 1082-1091. PMID: 27181681, PMCID: PMC4908195, DOI: 10.1016/j.ajhg.2016.03.022.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsHistone methyl transferase activityWhole-exome sequencingGenome-wide linkage analysisWild-type proteinPatent ductus arteriosusMethyl transferase activityEpigenetic regulationLoss of functionTranscriptional suppressorNuclear proteinsPremature differentiationMethyltransferase activityCommon congenital heart defectUndifferentiated stageIndependent mutationsDuctus arteriosusLinkage analysisIntracellular redistributionNumber of VSMCsPRDM6Smooth muscle cellsProteinMutationsDisease mechanisms
2007
EZH2 regulates the transcription of estrogen-responsive genes through association with REA, an estrogen receptor corepressor
Hwang C, Giri V, Wilkinson J, Wright C, Wilkinson A, Cooney K, Duckett C. EZH2 regulates the transcription of estrogen-responsive genes through association with REA, an estrogen receptor corepressor. Breast Cancer Research And Treatment 2007, 107: 235-242. PMID: 17453341, DOI: 10.1007/s10549-007-9542-7.Peer-Reviewed Original ResearchMeSH KeywordsCell DifferentiationCell Line, TumorDisease ProgressionDNA-Binding ProteinsEnhancer Elements, GeneticEnhancer of Zeste Homolog 2 ProteinEstradiolEstrogensHumansMicroscopy, FluorescencePolycomb Repressive Complex 2Polycomb-Group ProteinsProhibitinsReceptors, EstrogenRepressor ProteinsRNA InterferenceSignal TransductionTranscription FactorsTranscription, GeneticConceptsEstrogen-dependent transcriptionCellular differentiationReceptor activityPolycomb group (PcG) proteinsHistone methyltransferase activityDeregulated gene expressionActivity of EZH2Specific target genesNovel binding partnerBreast cancerEstrogen receptor corepressorPcG proteinsHistone modificationsTranscriptional repressionEstrogen-responsive genesTranscriptional corepressorGroup proteinsBreast cancer carcinogenesisZeste homolog 2Binding partnerTranscription factorsTarget genesHuman breast cancerEstrogen receptor activityMethyltransferase activity
2001
The Highly Conserved Protein Methyltransferase, Skb1, Is a Mediator of Hyperosmotic Stress Response in the Fission YeastSchizosaccharomyces pombe *
Bao S, Qyang Y, Yang P, Kim H, Du H, Bartholomeusz G, Henkel J, Pimental R, Verde F, Marcus S. The Highly Conserved Protein Methyltransferase, Skb1, Is a Mediator of Hyperosmotic Stress Response in the Fission YeastSchizosaccharomyces pombe *. Journal Of Biological Chemistry 2001, 276: 14549-14552. PMID: 11278267, DOI: 10.1074/jbc.c100096200.Peer-Reviewed Original ResearchConceptsHyperosmotic stress responseProtein methyltransferase activityS. pombe cellsFission yeastStress responseCell polarityProtein methyltransferasePombe cellsHyperosmotic stressMethyltransferase activityCell endsSites of septationNormal growth conditionsPrevious genetic studiesP21-activated kinaseEvolutionary conservationProtein methyltransferasesFission YeastSchizosaccharomycesSubcellular targetingSKB1Mating responseShk1F-actinGenetic studiesCell growth
2000
PRMT1 Is the Predominant Type I Protein Arginine Methyltransferase in Mammalian Cells*
Tang J, Frankel A, Cook R, Kim S, Paik W, Williams K, Clarke S, Herschman H. PRMT1 Is the Predominant Type I Protein Arginine Methyltransferase in Mammalian Cells*. Journal Of Biological Chemistry 2000, 275: 7723-7730. PMID: 10713084, DOI: 10.1074/jbc.275.11.7723.Peer-Reviewed Original ResearchConceptsProtein arginine methyltransferase activityArginine methyltransferase activityMurine tissue extractsMammalian cellsRat1 cellsMethyltransferase activityType I protein arginine methyltransferasesType I protein arginine methyltransferaseHeterogeneous nuclear ribonucleoprotein A1Protein arginine methyltransferasesProtein arginine methyltransferaseFDH activityHigh molecular weight complexesDomain fusion proteinMolecular weight complexesMethyl donor substrateDimethylarginine residuesArginine methyltransferasesArginine methyltransferaseEucaryotic proteinsPRMT1 activityDehydrogenase proteinFusion proteinEnzyme activity presentWeight complexes
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