Role of MPSI Kinase and Yeast Spindle Pole Cycle

MPSI 激酶和酵母纺锤体极循环的作用

基本信息

  • 批准号:
    7904475
  • 负责人:
  • 金额:
    $ 12.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-08-31 至 2012-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Centrosomes are the organelles at mitotic spindle poles that organize microtubules essential for chromosome segregation. Assembly of nascent centrosomes is a tightly regulated process that occurs exactly once each cell cycle. Defects in this process can lead to centrosomal abnormalities, which are frequently observed in tumor cells and are thought to contribute to genetic instability, a hallmark of cellular transformation. Protein phosphorylation is a critical signal involved in centrosome assembly and function, though the molecular details are not well understood. Using the S. cerevisiae centrosome (the Spindle Pole Body, SPB) as a model system, we will identify phosphorylation events that are important to the controlled assembly of a functional organelle. Key events will be tested for conservation in vertebrate cells. The first specific aim of this proposal focuses on the effects phosphorylation has on an important regulator of centrosome duplication, the protein kinase Mps1. Mps1 is tightly regulated through the cell cycle; it is subject to ubiquitin mediated proteolysis by the APC, and stabilized by cyclin dependant kinase phosphorylation. We will test whether phosphorylation by Cdk and autophosphorylation directly prevents ubiquitination in vitro, and assay the in vivo consequences of Mps1 mutated at these sites. The second specific aim is designed to obtain a comprehensive map of the phosphorylation state of the SPB. Phosphorylation sites will be identified on purified SPBs by mass spectrometry. By isolating SPBs from synchronized cells, we will monitor changes in phosphorylation that occur at particular points in the cell cycle. In addition, we will phosphorylate isolated SPBs with candidate kinases to gain an understanding of their contribution to the overall phosphorylation state of the SPB. The final specific aim focuses on the conserved gamma-tubulin complex. Although vertebrate centrosomes and yeast SPBs are structurally distinct, components involved in the nucleation of microtubules are conserved. Once in vivo and in vitro gamma-tubulin complex phosphorylation sites are mapped, we will determine the effects of mutations in these sites on cells, and on the ability of the complex to nucleate microtubules in vitro. By understanding the role phosphorylation plays at centrosomes, we will gain important insights into how centrosome assembly is coordinated with the cell cycle, and how the fidelity of mitosis is maintained.
描述(由申请人提供):中心体是有丝分裂纺锤体极的细胞器,组织染色体分离所必需的微管。新生中心体的组装是一个严格调控的过程,每个细胞周期只发生一次。这一过程中的缺陷可导致中心体异常,这在肿瘤细胞中经常观察到,并被认为有助于遗传不稳定性,这是细胞转化的标志。蛋白质磷酸化是中心体组装和功能的关键信号,尽管分子细节还不清楚。使用鼠伤寒沙门氏作为一个模型系统,我们将确定磷酸化事件是重要的功能性细胞器的控制组装。将测试关键事件在脊椎动物细胞中的保守性。该提案的第一个具体目标集中在磷酸化对中心体复制的重要调节因子蛋白激酶Mps 1的影响上。Mps 1在细胞周期中受到严格调控;它受到APC介导的泛素蛋白水解,并通过细胞周期蛋白依赖性激酶磷酸化来稳定。我们将测试是否磷酸化的Cdk和自磷酸化直接阻止体外泛素化,并测定在这些网站突变的Mps 1在体内的后果。第二个具体目标是获得SPB磷酸化状态的综合图谱。将通过质谱法在纯化的SPB上鉴定磷酸化位点。通过从同步化细胞中分离SPB,我们将监测在细胞周期中特定点发生的磷酸化变化。此外,我们将磷酸化分离的SPB与候选激酶,以了解他们的贡献的整体磷酸化状态的SPB。最后的具体目标集中在保守的γ-微管蛋白复合物。虽然脊椎动物中心体和酵母SPB在结构上是不同的,参与微管成核的组件是保守的。一旦在体内和体外γ-微管蛋白复合物磷酸化位点被映射,我们将确定这些位点的突变对细胞的影响,以及复合物在体外使微管成核的能力。通过了解磷酸化在中心体中的作用,我们将对中心体组装如何与细胞周期协调以及有丝分裂的保真度如何维持获得重要的见解。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

MARK WINEY其他文献

MARK WINEY的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('MARK WINEY', 18)}}的其他基金

MIPS (Microtubule Inner Proteins) function in cilia and basal bodies
MIPS(微管内部蛋白)在纤毛和基底体中发挥作用
  • 批准号:
    10655224
  • 财政年份:
    2018
  • 资助金额:
    $ 12.48万
  • 项目类别:
EFHC gene function in ciliary axomenes.
EFHC 基因在睫状轴丝中的功能。
  • 批准号:
    9900028
  • 财政年份:
    2018
  • 资助金额:
    $ 12.48万
  • 项目类别:
EFHC gene function in ciliary axomenes.
EFHC 基因在睫状轴丝中的功能。
  • 批准号:
    10386664
  • 财政年份:
    2018
  • 资助金额:
    $ 12.48万
  • 项目类别:
The Yeast Centrosome - Structure Assembly & Function
酵母中心体 - 结构组装
  • 批准号:
    8668219
  • 财政年份:
    2014
  • 资助金额:
    $ 12.48万
  • 项目类别:
The Yeast Centrosome - Structure Assembly & Function
酵母中心体 - 结构组装
  • 批准号:
    9486545
  • 财政年份:
    2014
  • 资助金额:
    $ 12.48万
  • 项目类别:
The Yeast Centrosome - Structure Assembly & Function
酵母中心体 - 结构组装
  • 批准号:
    9073389
  • 财政年份:
    2014
  • 资助金额:
    $ 12.48万
  • 项目类别:
Molecular Interactions and Dynamics of the Yeast SPB Core Architecture
酵母 SPB 核心架构的分子相互作用和动力学
  • 批准号:
    8668223
  • 财政年份:
    2014
  • 资助金额:
    $ 12.48万
  • 项目类别:
Acquisition of a Transmission Electron Microscope
购买透射电子显微镜
  • 批准号:
    8246562
  • 财政年份:
    2012
  • 资助金额:
    $ 12.48万
  • 项目类别:
SPINDLE POLE BODY PHOSPHOPROTEOME
纺锤体磷酸化蛋白质组
  • 批准号:
    8365899
  • 财政年份:
    2011
  • 资助金额:
    $ 12.48万
  • 项目类别:
TETRAHYMENA BASAL BODY DUPLICATION
四膜虫基础体复制
  • 批准号:
    8362544
  • 财政年份:
    2011
  • 资助金额:
    $ 12.48万
  • 项目类别:

相似海外基金

Linkage of HIV amino acid variants to protective host alleles at CHD1L and HLA class I loci in an African population
非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
  • 批准号:
    502556
  • 财政年份:
    2024
  • 资助金额:
    $ 12.48万
  • 项目类别:
Olfactory Epithelium Responses to Human APOE Alleles
嗅觉上皮对人类 APOE 等位基因的反应
  • 批准号:
    10659303
  • 财政年份:
    2023
  • 资助金额:
    $ 12.48万
  • 项目类别:
Deeply analyzing MHC class I-restricted peptide presentation mechanistics across alleles, pathways, and disease coupled with TCR discovery/characterization
深入分析跨等位基因、通路和疾病的 MHC I 类限制性肽呈递机制以及 TCR 发现/表征
  • 批准号:
    10674405
  • 财政年份:
    2023
  • 资助金额:
    $ 12.48万
  • 项目类别:
An off-the-shelf tumor cell vaccine with HLA-matching alleles for the personalized treatment of advanced solid tumors
具有 HLA 匹配等位基因的现成肿瘤细胞疫苗,用于晚期实体瘤的个性化治疗
  • 批准号:
    10758772
  • 财政年份:
    2023
  • 资助金额:
    $ 12.48万
  • 项目类别:
Identifying genetic variants that modify the effect size of ApoE alleles on late-onset Alzheimer's disease risk
识别改变 ApoE 等位基因对迟发性阿尔茨海默病风险影响大小的遗传变异
  • 批准号:
    10676499
  • 财政年份:
    2023
  • 资助金额:
    $ 12.48万
  • 项目类别:
New statistical approaches to mapping the functional impact of HLA alleles in multimodal complex disease datasets
绘制多模式复杂疾病数据集中 HLA 等位基因功能影响的新统计方法
  • 批准号:
    2748611
  • 财政年份:
    2022
  • 资助金额:
    $ 12.48万
  • 项目类别:
    Studentship
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
诱导多能干细胞的基因组和表观基因组编辑用于研究骨关节炎风险等位基因
  • 批准号:
    10532032
  • 财政年份:
    2022
  • 资助金额:
    $ 12.48万
  • 项目类别:
Recessive lethal alleles linked to seed abortion and their effect on fruit development in blueberries
与种子败育相关的隐性致死等位基因及其对蓝莓果实发育的影响
  • 批准号:
    22K05630
  • 财政年份:
    2022
  • 资助金额:
    $ 12.48万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Investigating the Effect of APOE Alleles on Neuro-Immunity of Human Brain Borders in Normal Aging and Alzheimer's Disease Using Single-Cell Multi-Omics and In Vitro Organoids
使用单细胞多组学和体外类器官研究 APOE 等位基因对正常衰老和阿尔茨海默病中人脑边界神经免疫的影响
  • 批准号:
    10525070
  • 财政年份:
    2022
  • 资助金额:
    $ 12.48万
  • 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
  • 批准号:
    10689017
  • 财政年份:
    2022
  • 资助金额:
    $ 12.48万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了