Clk Kinases and Splicing Regulation

Clk 激酶和剪接调节

基本信息

  • 批准号:
    9356568
  • 负责人:
  • 金额:
    $ 31.55万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-06-01 至 2020-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract: While the proper selection of splice sites drives genomic diversity, adaptive growth and development, errors in splicing can have enormous detrimental effects on function and is now recognized as the underlying cause for many human diseases. Indeed, splicing errors are associated with muscular dystrophy, Alzheimer's disease, Parkinsonism, psychiatric disorders, ataxias and cancers making the study of factors that control splice-site selection vitally important for human health. Splicing occurs at the spliceosome, a macromolecular complex composed of several RNAs and numerous proteins. Critical to normal gene splicing is the proper selection of the 5'-3' splice sites, events that occur early in the development of the spliceosome and whose specificity is guided by an essential family of splicing factors known as SR proteins. The phosphorylation states of SR proteins directly impact their subcellular localization and splicing activities but our understanding of how these different forms are attained is, at best, incomplete. The CLK family of protein kinases phosphorylates SR proteins and mobilizes them to sites of active gene splicing. The CLKs differ from many classic protein kinases in that they lack a docking groove for substrate binding but instead contain a disordered N-terminal extension that we showed attaches to the SR protein. In this proposal we will explore the role of the N-terminus for the mobilization of CLK1 and recognition of SR proteins in the nucleus using a wide array of in vivo and in vitro experiments. We will study the effects of CLK-dependent phosphorylation on SR protein conformation, subcellular localization, and interactions with critical mediators of splice-site selection in the spliceosome. The larger goal of this proposal is to define CLK function at both biological and biochemical levels so that we can better understand the mechanisms of human diseases associated with errors in splicing.
项目总结/文摘:

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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JOSEPH ADAMS其他文献

JOSEPH ADAMS的其他文献

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{{ truncateString('JOSEPH ADAMS', 18)}}的其他基金

Clk Kinases and Splicing Regulation
Clk 激酶和剪接调节
  • 批准号:
    8827803
  • 财政年份:
    2012
  • 资助金额:
    $ 31.55万
  • 项目类别:
Clk Kinases and Splicing Regulation
Clk 激酶和剪接调节
  • 批准号:
    8471724
  • 财政年份:
    2012
  • 资助金额:
    $ 31.55万
  • 项目类别:
Clk Kinases and Splicing Regulation
Clk 激酶和剪接调节
  • 批准号:
    8638029
  • 财政年份:
    2012
  • 资助金额:
    $ 31.55万
  • 项目类别:
Clk Kinases and Splicing Regulation
Clk 激酶和剪接调节
  • 批准号:
    8294209
  • 财政年份:
    2012
  • 资助金额:
    $ 31.55万
  • 项目类别:
Clk Kinases and Splicing Regulation
Clk 激酶和剪接调节
  • 批准号:
    9177458
  • 财政年份:
    2012
  • 资助金额:
    $ 31.55万
  • 项目类别:
Coordination of SR Protein Phosphorylation and RNA Splicing
SR 蛋白磷酸化和 RNA 剪接的协调
  • 批准号:
    7913861
  • 财政年份:
    2009
  • 资助金额:
    $ 31.55万
  • 项目类别:
Regulatory Pathways of SR Protein Kinases
SR蛋白激酶的调控途径
  • 批准号:
    8503353
  • 财政年份:
    2004
  • 资助金额:
    $ 31.55万
  • 项目类别:
Role of protein phosphorylation in RNA splicing
蛋白质磷酸化在 RNA 剪接中的作用
  • 批准号:
    6845233
  • 财政年份:
    2004
  • 资助金额:
    $ 31.55万
  • 项目类别:
Regulatory Pathways of SR Protein Kinases
SR蛋白激酶的调控途径
  • 批准号:
    9235874
  • 财政年份:
    2004
  • 资助金额:
    $ 31.55万
  • 项目类别:
Role of protein phosphorylation in RNA splicing
蛋白质磷酸化在 RNA 剪接中的作用
  • 批准号:
    7171542
  • 财政年份:
    2004
  • 资助金额:
    $ 31.55万
  • 项目类别:

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健康和疾病中剪接位点选择的机制
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  • 财政年份:
    2021
  • 资助金额:
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  • 项目类别:
Uncovering Mechanisms of 5' Splice Site Fidelity
揭示 5 剪接位点保真度的机制
  • 批准号:
    10532793
  • 财政年份:
    2020
  • 资助金额:
    $ 31.55万
  • 项目类别:
How do RNA-binding proteins control splice site selection?
RNA 结合蛋白如何控制剪接位点选择?
  • 批准号:
    BB/T000627/1
  • 财政年份:
    2020
  • 资助金额:
    $ 31.55万
  • 项目类别:
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Mechanism of Splice Site Recognition by the U2AF/SF1 Protein Complex
U2AF/SF1 蛋白复合物的剪接位点识别机制
  • 批准号:
    553974-2020
  • 财政年份:
    2020
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    $ 31.55万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Uncovering Mechanisms of 5' Splice Site Fidelity
揭示 5 剪接位点保真度的机制
  • 批准号:
    10316181
  • 财政年份:
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    $ 31.55万
  • 项目类别:
Mechanisms of Splice Site Selection in Health and Disease
健康和疾病中剪接位点选择的机制
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  • 项目类别:
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  • 财政年份:
    2019
  • 资助金额:
    $ 31.55万
  • 项目类别:
Mechanisms of Splice Site Selection in Health and Disease
健康和疾病中剪接位点选择的机制
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  • 财政年份:
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  • 资助金额:
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