Mechanism of Auxin Action
生长素作用机制
基本信息
- 批准号:7655068
- 负责人:
- 金额:$ 34.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1989
- 资助国家:美国
- 起止时间:1989-08-01 至 2013-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressArabidopsisAuxinsBindingBiochemicalBiochemical GeneticsBiological ProcessCell physiologyComparative StudyComplexConstitutionCyclophilinsDefectDiseaseEvolutionF-Box ProteinsFamilyFamily memberFloorGene TargetingGeneticGenomeGluesGoalsGrantHealthHormonesHumanHydrophobic InteractionsIn VitroKnowledgeLocationMalignant NeoplasmsModelingMolecularPathway interactionsPerceptionPhylogenetic AnalysisPhyscomitrellaPlant Growth RegulatorsPlantsProcessProteinsRegulationRoleSeriesSignal TransductionSpecificityStructural ModelsStructureTestingTomatoesTranscription CoactivatorTranscription Repressor/CorepressorUbiquitinWorkbasecell growth regulationgenome wide association studyhuman diseasein vivoinsightmembermulticatalytic endopeptidase complexnovelplant growth/developmentpromoterprotein complexprotein degradationpublic health relevancereceptorresearch studysensortranscription factorubiquitin-protein ligase
项目摘要
DESCRIPTION (provided by applicant): The plant hormone auxin is involved in many, perhaps all, aspects of plant growth and development. Auxin acts by stimulating the degradation of a family of transcriptional repressors called the Aux/IAA proteins, a process that requires the ubiquitin protein ligase (E3) SCFTIR1. During the last grant period we showed that auxin binds directly to the F-box protein TIR1, the substrate binding subunit in an E3 called SCFTIR1. Auxin binding stabilizes the interaction between SCFTIR1 and the Aux/IAA proteins. This is a novel mechanism of both hormone perception and E3 regulation. In addition we showed that TIR1 binds an InsP6 molecule and suggest that InsP6 may be required for TIR1 structure and/or function. Further we demonstrated that TIR1 is one of 6 related auxin sensor F-box proteins, collectively called the AFBs. The current proposal has five specific aims. The first is to investigate the molecular mechanism of auxin perception by TIR1. Based on our previous work, we propose that auxin acts like molecular glue to stabilize the TIR1- Aux/IAA complex. Biochemical studies will be performed to test various aspects of this model. In addition, we will determine the importance of InsP6 for TIR1 function. The second Aim is to characterize the biochemical diversity of the AFB proteins. A series of in vitro studies will be performed to characterize auxin and Aux/IAA binding to each member of the family. The significance of any specific interactions will be determined in vivo. The third Aim is to identify and characterize protein complexes containing TIR1 and/or the Aux/IAA proteins IAA28 with the goal of obtaining further information on the regulation of TIR1. In addition, this aim will provide additional information on the specificity of TIR1 and Aux/IAA interactions and the cellular location of TIR1-Aux/IAA complex formation. Aim four is to determine the function of cyclophilin molecules in auxin action. The fifth Aim is to characterize the auxin transcriptional network with a focus on two transcription factors called ARF5 and ARF7. These studies address a number of key issues in cellular regulation and will have important implications for human health. The ubiquitin pathway and SCF E3s in particular, are involved in diverse disease processes including numerous cancers. Because SCFTIR1 is one of the best-characterized E3 complexes in any species, this work provides a unique opportunity to advance our understanding of this critical aspect of human disease PUBLIC HEALTH RELEVANCE: Protein degradation by the ubiquitin/proteasome pathway is a central aspect of cellular regulation. Defects in the pathway contribute to many disease processes including cancers. This study will advance our understanding of the ubiquitin/proteasome pathway in cell function.
植物激素生长素参与植物生长和发育的许多方面,也许是所有方面。生长素通过刺激称为Aux/IAA蛋白的转录抑制因子家族的降解而起作用,该过程需要泛素蛋白连接酶(E3)SCFTIR 1。在上一个资助期间,我们发现生长素直接与F-box蛋白TIR 1结合,F-box蛋白TIR 1是E3中的底物结合亚基,称为SCFTIR 1。生长素结合稳定SCFTIR 1和Aux/IAA蛋白之间的相互作用。这是激素感知和E3调节的新机制。此外,我们发现,TIR 1结合InsP 6分子,并建议InsP 6可能需要TIR 1的结构和/或功能。我们进一步证明了TIR 1是6个相关的生长素传感器F-box蛋白之一,统称为AFB。目前的建议有五个具体目标。第一部分是研究TIR 1感受生长素的分子机制。基于我们以前的工作,我们提出生长素的行为像分子胶水,以稳定的TIR 1- Aux/IAA复合物。将进行生化研究以测试该模型的各个方面。此外,我们将确定InsP 6对TIR 1功能的重要性。第二个目的是表征AFB蛋白的生化多样性。将进行一系列体外研究以表征生长素和Aux/IAA与该家族每个成员的结合。将在体内确定任何特定相互作用的显著性。第三个目的是鉴定和表征含有TIR 1和/或Aux/IAA蛋白IAA 28的蛋白质复合物,目的是获得关于TIR 1调节的进一步信息。此外,这一目标将提供更多的信息,TIR 1和Aux/IAA相互作用的特异性和TIR 1-Aux/IAA复合物形成的细胞定位。目的四是确定亲环素分子在生长素作用中的功能。第五个目标是表征生长素转录网络,重点是两个转录因子ARF 5和ARF 7。这些研究解决了细胞调节中的一些关键问题,并将对人类健康产生重要影响。泛素途径和SCF E3尤其参与包括许多癌症在内的多种疾病过程。由于SCFTIR 1是任何物种中最具特征的E3复合物之一,这项工作提供了一个独特的机会,以促进我们对人类疾病这一关键方面的理解。该途径的缺陷导致许多疾病过程,包括癌症。这项研究将促进我们对细胞功能中泛素/蛋白酶体通路的理解。
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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{{ truncateString('MARK A ESTELLE', 18)}}的其他基金
Novel auxin signaling components and pathways.
新型生长素信号传导成分和途径。
- 批准号:
10398201 - 财政年份:2021
- 资助金额:
$ 34.32万 - 项目类别:
Novel auxin signaling components and pathways.
新型生长素信号传导成分和途径。
- 批准号:
10206841 - 财政年份:2021
- 资助金额:
$ 34.32万 - 项目类别:
Novel auxin signaling components and pathways.
新型生长素信号传导成分和途径。
- 批准号:
10797344 - 财政年份:2021
- 资助金额:
$ 34.32万 - 项目类别:
Novel auxin signaling components and pathways.
新型生长素信号传导成分和途径。
- 批准号:
10614965 - 财政年份:2021
- 资助金额:
$ 34.32万 - 项目类别:
FUNCTION OF AXR1 AND AXR1-LIKE GENES IN ARABIDOPSIS
拟南芥中 AXR1 和 AXR1 样基因的功能
- 批准号:
2857134 - 财政年份:1989
- 资助金额:
$ 34.32万 - 项目类别:
FUNCTION OF AXR1 AND AXR1 LIKE GENES IN ARABIDOPSIS
拟南芥中 AXR1 和 AXR1 样基因的功能
- 批准号:
6081454 - 财政年份:1989
- 资助金额:
$ 34.32万 - 项目类别:
MOLECULAR GENETICS OF AUXIN ACTION IN ARABIDOPSIS
拟南芥生长素作用的分子遗传学
- 批准号:
6490030 - 财政年份:1989
- 资助金额:
$ 34.32万 - 项目类别:
FUNCTION OF AXR1 AND AXR1-LIKE GENES IN ARABIDOPSIS
拟南芥中 AXR1 和 AXR1 样基因的功能
- 批准号:
2022364 - 财政年份:1989
- 资助金额:
$ 34.32万 - 项目类别:
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