Regulation of CBP by Synaptic Activity

突触活动对 CBP 的调节

基本信息

  • 批准号:
    6418693
  • 负责人:
  • 金额:
    $ 12.97万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2002
  • 资助国家:
    美国
  • 起止时间:
    2002-01-07 至 2005-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Activity-regulated gene expression plays a fundamental role in both the remodeling of synaptic circuitry and in neuronal survival. Activity-dependent increases in intracellular Ca2+ trigger the expression of hundreds or perhaps thousands of genes. The cAMP response element (CRE) was identified as a major Ca2+ responsive element via analysis of immediate early gene (IEGs) promoters and many if not most Ca2+ responsive promoters contain CREs. The basic leucine zipper transcription factor, CREB, binds to the CRE as a dimer and can be activated by Ca2+, cAMP/PKA, and growth factor signaling pathways. The transcription factor CREB is a major target of activity-induced Ca2+ influx and is a key regulator of both neuronal survival and adaptive synaptic plasticity. Nevertheless, the mechanisms by which Ca2+ activates CREB have not been clearly elucidated. It is well established that PKA phosphorylates Ser 133 of CREB and creates a phospho-serine docking motif that recruits its coactivator CBP (or the homologue, p300). Recruitment of CBP is thought to enhance transcriptional activation either via its association with the general transcriptional machinery or via its intrinsic histone acetyltransferase activity. Although activity-induced Ca2+ influx is widely believed to regulate CREB function in an analogous manner, the signaling cascades that promote CBP recruitment and transcriptional activation have not been clearly defined. A major theme of this proposal is to determine whether the PKA-CREB-CBP paradigm also pertains to Ca2+-activated transcription. Thus, an initial goal of this study will be to determine whether neuronal activity induces the recruitment of CBP to CREB and whether CBP recruitment is required for transcriptional activation. Four specific aims are proposed. (1) Determine whether synaptic activity induces the recruitment of CBP to CREB in neurons and whether recruitment of CBP is sufficient for full transcriptional activation. (2) Decipher the activity-regulated signaling cascades that promote the phosphorylation and activation of CREB and CBP. (3) Determine how synaptic activity and Ca2+ influx regulate CBP function. (4) Analyze the regulation of CBP and CREB function in mice deficient for CaM kinase IV. This study seeks to dissect the biochemical events result in synaptic activity-mediated phosphorylation of CREB, recruitment of CBP, and "activation" of CBP-dependent transcription. Gaining insight into the mechanisms of activity-mediated transcription has relevance in the treatment of neurodegenerative pathologies that may result from excitotoxic cell death or apoptosis. Through a mentored career development plan, the Principal Investigator will gain an enhanced capacity to be productive in the field of molecular neurobiology with a focus on gene regulation. This will be accomplished by conducting the above described research, attending and presenting at local and national seminars and meetings, and participating in courses teaching molecular biology and neurophysiology techniques.
描述(由申请人提供):

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 }}

SOREN IMPEY其他文献

SOREN IMPEY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('SOREN IMPEY', 18)}}的其他基金

Activity-dependent microRNA expression and function in the mature nervous system
成熟神经系统中活性依赖性的 microRNA 表达和功能
  • 批准号:
    8144331
  • 财政年份:
    2010
  • 资助金额:
    $ 12.97万
  • 项目类别:
Activity-dependent microRNA expression and function in the mature nervous system
成熟神经系统中活性依赖性的 microRNA 表达和功能
  • 批准号:
    8730236
  • 财政年份:
    2010
  • 资助金额:
    $ 12.97万
  • 项目类别:
Activity-dependent microRNA expression and function in the mature nervous system
成熟神经系统中活性依赖性的 microRNA 表达和功能
  • 批准号:
    8325141
  • 财政年份:
    2010
  • 资助金额:
    $ 12.97万
  • 项目类别:
Activity-dependent microRNA expression and function in the mature nervous system
成熟神经系统中活性依赖性的 microRNA 表达和功能
  • 批准号:
    8050430
  • 财政年份:
    2010
  • 资助金额:
    $ 12.97万
  • 项目类别:
Activity-dependent microRNA expression and function in the mature nervous system
成熟神经系统中活性依赖性的 microRNA 表达和功能
  • 批准号:
    8531361
  • 财政年份:
    2010
  • 资助金额:
    $ 12.97万
  • 项目类别:
Genomic-wide Analysis of Oct 3/4 and Nanog Targets
Oct 3/4 和 Nanog 目标的全基因组分析
  • 批准号:
    7629633
  • 财政年份:
    2006
  • 资助金额:
    $ 12.97万
  • 项目类别:
Genomic-wide Analysis of Oct 3/4 and Nanog Targets
Oct 3/4 和 Nanog 目标的全基因组分析
  • 批准号:
    7858545
  • 财政年份:
    2006
  • 资助金额:
    $ 12.97万
  • 项目类别:
Genomic-wide Analysis of Oct 3/4 and Nanog Targets
Oct 3/4 和 Nanog 目标的全基因组分析
  • 批准号:
    7144463
  • 财政年份:
    2006
  • 资助金额:
    $ 12.97万
  • 项目类别:
Genomic-wide Analysis of Oct 3/4 and Nanog Targets
Oct 3/4 和 Nanog 目标的全基因组分析
  • 批准号:
    7455921
  • 财政年份:
    2006
  • 资助金额:
    $ 12.97万
  • 项目类别:
Genomic-wide Analysis of Oct 3/4 and Nanog Targets
Oct 3/4 和 Nanog 目标的全基因组分析
  • 批准号:
    7248722
  • 财政年份:
    2006
  • 资助金额:
    $ 12.97万
  • 项目类别:

相似海外基金

Novel functions of the evolutionarily conserved cAMP response element-binding protein (CREB): Identifying and characterizing tissue-specific CREB targets that coordinate reproduction, metabolic status, and aging
进化上保守的 cAMP 反应元件结合蛋白 (CREB) 的新功能:识别和表征协调生殖、代谢状态和衰老的组织特异性 CREB ​​靶标
  • 批准号:
    362225
  • 财政年份:
    2016
  • 资助金额:
    $ 12.97万
  • 项目类别:
    Fellowship Programs
Novel functions of the evolutionarily conserved cAMP response element-binding protein (CREB): Identifying and characterizing tissue-specific CREB targets that coordinate whole-organismal decisions related to metabolic status, reproduction, and aging
进化上保守的 cAMP 反应元件结合蛋白 (CREB) 的新功能:识别和表征组织特异性 CREB ​​目标,协调与代谢状态、繁殖和衰老相关的整个生物体决策
  • 批准号:
    358935
  • 财政年份:
    2016
  • 资助金额:
    $ 12.97万
  • 项目类别:
    Fellowship Programs
PROTEIN SYNTHESIS, CAMP RESPONSE ELEMENT BINDING PROTEIN
蛋白质合成,CAMP 反应元件结合蛋白
  • 批准号:
    6402827
  • 财政年份:
    2001
  • 资助金额:
    $ 12.97万
  • 项目类别:
PROTEIN SYNTHESIS, CAMP RESPONSE ELEMENT BINDING PROTEIN
蛋白质合成,CAMP 反应元件结合蛋白
  • 批准号:
    6187628
  • 财政年份:
    2000
  • 资助金额:
    $ 12.97万
  • 项目类别:
PROTEIN SYNTHESIS, CAMP RESPONSE ELEMENT BINDING PROTEIN
蛋白质合成,CAMP 反应元件结合蛋白
  • 批准号:
    6019898
  • 财政年份:
    1999
  • 资助金额:
    $ 12.97万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了