Biophysical studies of oncogenic Cdc42Hs constructs
致癌 Cdc42Hs 构建体的生物物理学研究
基本信息
- 批准号:7912935
- 负责人:
- 金额:$ 14.36万
- 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:2007-09-10 至 2012-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAffectAffinityAmino AcidsAntineoplastic AgentsAreaBehaviorBindingBinding ProteinsBiologicalBiological ProcessBreastCell ProliferationCell Signaling ProcessCell physiologyChimera organismCollaborationsColonDataData AnalysesDefectDevelopmentDevelopment PlansDissociationDrug DesignEventExhibitsFluorescenceFluorescence SpectroscopyForms ControlsFosteringFoundationsFutureGTP BindingGTP-Binding ProteinsGoalsGuanine Nucleotide Dissociation InhibitorsGuanine NucleotidesGuanosine TriphosphateGuanosine Triphosphate PhosphohydrolasesHRAS geneHumanHydrolysisInvestigationLeadLightLungMalignant NeoplasmsMediatingMentorsMethodsModelingMolecularMolecular ConformationMolecular MedicineMutationNMR SpectroscopyNatureNeoplasm MetastasisNucleotidesOncogenicPeptidesPharmaceutical PreparationsPhasePhosphotransferasesPreparationProceduresProcessProtein RegionProteinsRelative (related person)ResearchSignal PathwaySignal TransductionSignal Transduction PathwaySignaling ProteinSolutionsSpecificityStructureStructure-Activity RelationshipTechniquesTestingTherapeuticTimeTumor Cell InvasionUniversitiesWorkbasecancer cellcancer therapycareercareer developmentcell transformationcell typechemotherapydefined contributiondesignexperiencegenetic regulatory proteinguanine nucleotide binding proteininhibitor/antagonistinnovationmembermetaplastic cell transformationmutantprogramsprotein protein interactionprotein structureras Proteinsrhostructural biologysuccesstherapeutic targettooltumorigenesis
项目摘要
DESCRIPTION (provided by applicant): Cdc42Hs, a member of the Ras superfamily signal transduction proteins, binds guanine nucleotides and acts as a molecular timing switch in multiple signal transduction pathways. This proposal is centered around studying the structure and dynamics of Cdc42Hs forms associated with its oncogenic potential and will provide atomic level information into mechanisms that regulate this activity. The Cdc42Hs constructs that will be studied are, A) Cdc42Hs(nucleotide-free) and, B) Cdc42Hs(F28L_?L8). Defining the structure and dynamics of the nucleotide-depleted form of Cdc42Hs will shed light on the conformation(s) of Cdc42Hs that facilitate the binding of protein effectors, such as Dbl, that stimulate oncogenic activity. The study of the structure and dynamics of Cdc42Hs(F28L_?L8) should reveal information on interactions in Cdc42Hs that block oncogenic activity caused by the single mutant Cdc42Hs(F28L).
The immediate goals of this research are to use NMR and fluorescence as structural techniques to gain a better understanding of the processes by which changes in Cdc42Hs and its interaction with regulators affect various important signal transduction pathways that lead to cancer. The long-term goals of this proposed research are to gain a better understanding of how protein structure and dynamics correlate with aberrant cell function, which will lay the foundation for future research into the development of a rational anti-cancer drug design program. Cdc42Hs is a member of the Ras superfamily of proteins, which have been implicated in cancers in the colon, breasts, and lungs. These studies will provide information on particular aspects of specific cell-signaling processes that may be subsequently used in the development of new anti-cancer treatments that are specific and may be less toxic than traditional chemotherapy approaches. I have a background in the use of fluorescence spectroscopy in the study of biological molecules and have used NMR spectroscopy to study structure of small peptides in solution. The mentored phase of this proposal will provide me with the opportunity to gain experience in several uses of these techniques that have not yet been mastered that will be crucial to my transition to independent investigation. The Department of Molecular Medicine at Cornell University has great experience in the area of applying physical methods to biological processes, and in particular, signal transduction. It is an excellent setting for this project, and also to foster the development of my career. The research career development plan of this proposal is two-phased. Phase I (Mentored) will allow for the study of the nucleotide-free construct of Cdc42Hs. The experience with the structural tools, data analysis procedures, and scientific collaboration in this phase will foster the necessary preparation for a successful transition into Phase II (Independent), during which time I will study the structure and dynamics of Cdc42Hs(F28L_?L8), leading to further research in the structural biology of biomolecules related to cancer.
描述(由申请人提供):Cdc42Hs是Ras超家族信号转导蛋白的一员,与鸟嘌呤核苷酸结合,在多种信号转导途径中作为分子定时开关。本研究的重点是研究Cdc42Hs的结构和动力学及其致癌潜能,并将为调控这种活性的机制提供原子水平的信息。将研究的Cdc42Hs结构为A) Cdc42Hs(无核苷酸)和B) Cdc42Hs(F28L_?L8)。定义Cdc42Hs的核苷酸耗尽形式的结构和动力学将揭示Cdc42Hs的构象,这些构象促进了蛋白质效应物(如Dbl)的结合,从而刺激了致癌活性。Cdc42Hs(F28L_?)的结构和动力学研究L8)应该揭示Cdc42Hs中阻断单突变Cdc42Hs(F28L)引起的致癌活性的相互作用的信息。
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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PAUL Damien ADAMS其他文献
PAUL Damien ADAMS的其他文献
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{{ truncateString('PAUL Damien ADAMS', 18)}}的其他基金
Monovalent Nanocrystals for Biomedical Imaging
用于生物医学成像的单价纳米晶体
- 批准号:
7904025 - 财政年份:2009
- 资助金额:
$ 14.36万 - 项目类别:
Biophysical studies of oncogenic Cdc42Hs constructs
致癌 Cdc42Hs 构建体的生物物理研究
- 批准号:
7940198 - 财政年份:2009
- 资助金额:
$ 14.36万 - 项目类别:
Monovalent Nanocrystals for Biomedical Imaging
用于生物医学成像的单价纳米晶体
- 批准号:
7707451 - 财政年份:2009
- 资助金额:
$ 14.36万 - 项目类别:
Biophysical studies of oncogenic Cdc42Hs constructs
致癌 Cdc42Hs 构建体的生物物理研究
- 批准号:
7667244 - 财政年份:2007
- 资助金额:
$ 14.36万 - 项目类别:
Biophysical studies of oncogenic Cdc42Hs constructs
致癌 Cdc42Hs 构建体的生物物理研究
- 批准号:
8103146 - 财政年份:2007
- 资助金额:
$ 14.36万 - 项目类别:
Biophysical studies of oncogenic Cdc42Hs constructs
致癌 Cdc42Hs 构建体的生物物理研究
- 批准号:
7494160 - 财政年份:2007
- 资助金额:
$ 14.36万 - 项目类别:
Biophysical studies of oncogenic Cdc42Hs constructs
致癌 Cdc42Hs 构建体的生物物理研究
- 批准号:
7201874 - 财政年份:2007
- 资助金额:
$ 14.36万 - 项目类别:
PROJECT 1 - LAWRENCE BERKELEY LAB - PHENIX
项目 1 - 劳伦斯伯克利实验室 - 凤凰城
- 批准号:
7208309 - 财政年份:2006
- 资助金额:
$ 14.36万 - 项目类别:
PROJECT 1 - LAWRENCE BERKELEY LAB - PHENIX
项目 1 - 劳伦斯伯克利实验室 - 凤凰城
- 批准号:
7673541 - 财政年份:
- 资助金额:
$ 14.36万 - 项目类别:
PROJECT 1 - LAWRENCE BERKELEY LAB - PHENIX
项目 1 - 劳伦斯伯克利实验室 - 凤凰城
- 批准号:
7908729 - 财政年份:
- 资助金额:
$ 14.36万 - 项目类别:
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