Ubiquitin-dependent mechanisms of tissue-specific cell cycle control
组织特异性细胞周期控制的泛素依赖性机制
基本信息
- 批准号:7431182
- 负责人:
- 金额:$ 229.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-09-30 至 2012-08-31
- 项目状态:已结题
- 来源:
- 关键词:26S proteasomeAccountingAchievementActive SitesAddressAdenomatous Polyposis Coli ProteinAdverse effectsAffectAffinityAffinity ChromatographyAliquotAneuploidyAnimal ModelAnimalsAntimitotic AgentsApoptosisArchitectureAttentionAutomationAutoradiographyAwardBRCA1 geneBacteriaBindingBiochemicalBiochemistryBiological AssayBiologyBostonBoxingBreastBreast Cancer CellBypassCDC2 Protein KinaseCDKN1A geneCaenorhabditis elegansCaliforniaCatalytic DomainCause of DeathCdc25B proteinCell CountCell CycleCell Cycle ArrestCell Cycle CheckpointCell Cycle DeregulationCell Cycle ProgressionCell Cycle RegulationCell Cycle StageCell ExtractsCell LineCell divisionCellsCellular biologyCessation of lifeChargeChemicalsCherry - dietaryChromosome CondensationClassCollaborationsColonColon CarcinomaComplexConditionConserved SequenceCultured CellsCyclin D1Cyclin ECyclin-Dependent Kinase InhibitorCyclin-Dependent KinasesCyclinsCysteineCytokinesisDNADNA DamageDNA RepairData AnalysesDefectDepthDeubiquitinating EnzymeDeubiquitinationDevelopmentDevelopmental ProcessDifferentiation AntigensDimethyl SulfoxideDiseaseDissectionDominant-Negative MutationDown-RegulationDrosophila genusDrug CombinationsDrug Delivery SystemsElementsEmbryoEmployee StrikesEmploymentEnd Point AssayEndocytosisEnergy TransferEnvironmentEnzyme Inhibitor DrugsEnzyme InhibitorsEnzymesEpidermal Growth Factor ReceptorErythropoiesisEssential GenesEstersEthylmaleimideEukaryotaEukaryotic CellEventFailureFamily memberFigs - dietaryFluorescenceForcible intercourseGene ExpressionGenesGeneticGenetic ScreeningGenetic TranscriptionGenus ColaGerm-Line MutationGiant CellsGleevecGoalsGreen Fluorescent ProteinsGrowthGrowth FactorGrowth Factor ReceptorsHela CellsHematopoiesisHematopoieticHereditary DiseaseHistonesHourHumanHuman ResourcesImage AnalysisImmunoprecipitationIn VitroIncubatedIndividualInsectaInstitutionInterphaseInterphase CellInvestigationKnock-outKnockout MiceKnowledgeLabelLaboratoriesLeadLeftLibrariesLifeLinkLungLymphocyteLysineMalignant NeoplasmsMalignant neoplasm of ovaryMammalsMasksMass Spectrum AnalysisMeasurementMeasuresMediatingMeiosisMetabolic stressMicroarray AnalysisMicroscopeMicrotubulesMiniaturizationMitosisMitoticModelingModificationMonitorMonoubiquitinationMorphologyMusMuscleMutateMutationNatureNeuronsNormal tissue morphologyNuclearNumbersObject AttachmentOncogenesOncogenicOocytesOrganismOrganogenesisOvarianPaclitaxelPathway interactionsPeptidesPharmaceutical PreparationsPhasePhenotypePhosphoric Monoester HydrolasesPhosphorylationPhosphotransferasesPoint MutationProblem SolvingProcessProtein OverexpressionProteinsProteolysisPublicationsQualifyingRadiolabeledReactionReaderRecombinant ProteinsRecombinantsRecruitment ActivityRegulationResearchResearch DesignResearch PersonnelResistanceRetinoblastomaRoleRunningScienceScientistScoreScreening procedureSelection CriteriaSerineSignal PathwaySignal TransductionSirolimusSister ChromatidSmall Interfering RNASpecificityStaining methodStainsSterilityStructureSurfaceSystemTP53 geneTechniquesTestingTherapeuticTimeTimeLineTissuesToxinTranscriptional ActivationTransfectionTranslationsUbiquitinUbiquitinationUnited StatesUniversitiesUp-RegulationWeekWingYeastsabstractingbasec-myc GenescDNA Librarycancer cellcell typecellular imagingchemotherapyenzyme mechanismenzyme substrateexperienceexpression cloningfluorophoregenetic regulatory proteinhigh throughput screeninghuman CCNE1 proteinhuman PTTG1 proteinhuman diseaseimprovedinhibitor/antagonistinnovationinsightknockout genemedical schoolsmemberminiaturizemonastrolmulticatalytic endopeptidase complexmutantnetwork modelsnoveloncoprotein p21p27 Cell Cycle Proteinp27 Enzyme Inhibitorprogramsprotein degradationradiotracerreconstitutionresearch studyroscovitinesmall hairpin RNAsmall moleculesmall molecule librariesthioestertissue/cell culturetooltranscription factortrophoblasttumortumorigenesisubiquitin ligasewastingwortmannin
项目摘要
This proposal describes an integrated approach to identify modules of tissue-specific cell
cycle control. Despite clear evidence for tissue-specificity in proliferation and the
outstanding importance of tissue-specific cell cycle regulation for development and
disease, the underlying mechanisms have not been uncovered. The identification and
characterization of tissue-specific modules in proliferative networks will not only provide
deep insight into development of multicellular organisms and tumorigenesis, but also lay
the groundwork for the discovery of tissue-specific chemotherapeutics.
Because of the crucial role of ubiquitination in cell cycle control, the tissue-specific
expression of ubiquitination enzymes, the frequent misregulation of ubiquitination in
cancer, and the enzymatic nature of ubiquitination, we will focus the dissection of tissue-
specific cell cycle regulation on members of the ubiquitination machinery.
Using synthetic lethality siRNA screens in different cell lines, we will identify
ubiquitination enzymes required for tissue-specific cell cycle control. By isolating
substrates of these enzymes unique to a certain tissue, we will delineate pathways
underlying cell cycle regulation in this tissue. Finally, by developing and miniaturizing
quantifiable ubiquitination assays, we will isolate small-molecule inhibitors that allow
further dissection of proliferative networks and may serve as lead structures for novel
tissue-specific chemotherapeutics.
We are convinced that this integrated approach using genetic discovery, biochemical
dissection, and inhibitor identification based on chemical biology will provide deep
insights into cell cycle and developmental regulation and lay the groundwork for novel,
innovative chemotherapeutics with improved tissue-specificity.
该建议描述了一种识别组织特异性细胞模块的集成方法
循环控制尽管有明确的证据表明,在增殖和细胞周期中存在组织特异性,
组织特异性细胞周期调节对发育的重要性,
疾病的潜在机制尚未被发现。确定和
在增殖网络中的组织特异性模块的表征将不仅提供
深入了解多细胞生物的发展和肿瘤发生,但也奠定了
为发现组织特异性化疗药物奠定了基础。
由于泛素化在细胞周期控制中的关键作用,
泛素化酶的表达,泛素化的频繁失调,
癌症,和泛素化的酶的性质,我们将集中解剖组织-
对泛素化机制成员的特异性细胞周期调控。
在不同的细胞系中使用合成的致死性siRNA筛选,我们将鉴定
组织特异性细胞周期控制所需的泛素化酶。通过隔离
底物的这些酶独特的某一组织,我们将描绘途径
在这个组织中潜在的细胞周期调节。最后,通过开发和
可量化的泛素化分析,我们将分离小分子抑制剂,
进一步解剖增殖网络,并可作为新的
组织特异性化疗药物。
我们相信,这种综合方法利用基因发现,生物化学,
解剖和抑制剂鉴定的基础上化学生物学将提供深入的
深入了解细胞周期和发育调控,并为新的,
具有改进的组织特异性的创新化疗药物。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Michael P Rape其他文献
Michael P Rape的其他文献
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{{ truncateString('Michael P Rape', 18)}}的其他基金
Function and regulation of the reductive stress response
还原应激反应的功能和调节
- 批准号:
10717394 - 财政年份:2023
- 资助金额:
$ 229.98万 - 项目类别:
Dissecting mechanisms of ubiquitination and deubiquitination in cell cycle contro
剖析细胞周期控制中泛素化和去泛素化的机制
- 批准号:
7847414 - 财政年份:2008
- 资助金额:
$ 229.98万 - 项目类别:
Dissecting Mechanisms of Ubiquitination and Deubiquitination in Cell Cycle Contro
剖析细胞周期控制中泛素化和去泛素化的机制
- 批准号:
8593301 - 财政年份:2008
- 资助金额:
$ 229.98万 - 项目类别:
Dissecting mechanisms of ubiquitination and deubiquitination in cell cycle contro
剖析细胞周期控制中泛素化和去泛素化的机制
- 批准号:
7350793 - 财政年份:2008
- 资助金额:
$ 229.98万 - 项目类别:
Dissecting mechanisms of ubiquitination and deubiquitination in cell cycle contro
剖析细胞周期控制中泛素化和去泛素化的机制
- 批准号:
8102982 - 财政年份:2008
- 资助金额:
$ 229.98万 - 项目类别:
Dissecting Mechanisms of Ubiquitination and Deubiquitination in Cell Cycle Contro
剖析细胞周期控制中泛素化和去泛素化的机制
- 批准号:
8440056 - 财政年份:2008
- 资助金额:
$ 229.98万 - 项目类别:
Dissecting mechanisms of ubiquitination and deubiquitination in cell cycle contro
剖析细胞周期控制中泛素化和去泛素化的机制
- 批准号:
7676844 - 财政年份:2008
- 资助金额:
$ 229.98万 - 项目类别:
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