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
- 来源:
- 关键词:3&apos Splice SiteActive SitesAffectAlzheimer&aposs DiseaseAtaxiaBindingBiochemicalBiologicalBiological AssayBiological ProcessC-terminalCell NucleusCell SurvivalCell physiologyCellsChemicalsComplexDataDevelopmentDipeptidesDiseaseDockingEnzymesEventFamilyFundingGenesGenomicsGoalsGrowth and Development functionHealthHumanImageIn VitroLinkMacromolecular ComplexesMalignant NeoplasmsMediator of activation proteinMental disordersMessenger RNAMethodsModificationMolecular ConformationMuscular DystrophiesN-terminalNatureNuclearParkinsonian DisordersPatternPhosphoric Monoester HydrolasesPhosphorylationPhosphotransferasesPhysiologicalProtein ConformationProtein FamilyProtein KinaseProtein phosphataseProteinsRNA SplicingRRM1 geneRRM2 geneRegulationRoleSTY kinaseSiteSpecificitySpliced GenesSpliceosomesStructureU1 Small Nuclear Ribonucleoproteinacrosome stabilizing factorbiophysical techniquesexperimental studygenome-widehuman diseasein vivoprolyl-serinepublic health relevancescaffoldseryl-proline
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)
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 }}
JOSEPH ADAMS其他文献
JOSEPH ADAMS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('JOSEPH ADAMS', 18)}}的其他基金
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:
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:
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:
相似海外基金
Mechanisms of Splice Site Selection in Health and Disease
健康和疾病中剪接位点选择的机制
- 批准号:
10797554 - 财政年份:2023
- 资助金额:
$ 31.55万 - 项目类别:
Quantitative and Predictive Analysis of 5' Splice Site Recognition by U1 snRNP using Massively Parallel Arrays
使用大规模并行阵列对 U1 snRNP 5 剪接位点识别进行定量和预测分析
- 批准号:
10460136 - 财政年份:2021
- 资助金额:
$ 31.55万 - 项目类别:
Quantitative and Predictive Analysis of 5' Splice Site Recognition by U1 snRNP using Massively Parallel Arrays
使用大规模并行阵列对 U1 snRNP 5 剪接位点识别进行定量和预测分析
- 批准号:
10311645 - 财政年份:2021
- 资助金额:
$ 31.55万 - 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:
Research Grant
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
- 资助金额:
$ 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:2020
- 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
- 批准号:
10769989 - 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
- 批准号:
10808389 - 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
- 批准号:
10585911 - 财政年份:2019
- 资助金额:
$ 31.55万 - 项目类别: