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
- 来源:
- 关键词:
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)
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{{ 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:
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