POSTTRANSCRIPTIONAL GENE REGULATION IN T CELL ACTIVATION
T 细胞激活中的转录后基因调控
基本信息
- 批准号:6604179
- 负责人:
- 金额:$ 30.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-07-01 至 2005-05-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (adapted from investigator's abstract): This application is
directed at understanding mechanisms of cytokine production in T cells at the
level of RNA structure and function. The regulation of immune function in T
cells at the level of messenger RNA stability is poorly understood. We will
focus on the role of the ELAV/Hu proteins in T cells by production of
HuR-deficient mice using the cre/lox mediated T cell knockout procedure.
Previously, we reported that ELAV proteins bind to and stabilize mRNAs encoding
growth regulatory proteins of the early-response gene (ERG) type. ERG mRNAs
encode protooncogenes and cytokines, which uniquely contain AU-rich instability
elements in their 3' untranslated regions to which the ELAV/Hu proteins bind.
Therefore, we will overexpress and under-express HuR in Jurkat T cells using
the Tet-inducible system and study their activation using the CD3/CD28 pathway
in which cytokine mRNAs have been shown previously to be stabilized. In
addition, an in vitro deadenylation/degradation system will be used to examine
the mechanisms by which HuR engages cytokine mRNAs in stability and
translation. We will use site-directed mutagenesis of HuR to determine
interactions critical for the expression of cytokine and ERG mRNAs during T
cell activation. Our hypothesis is that HuR is critical for T cell growth and
development by governing the expression of cytokine and ERG mRNAs through
interactions with the translational apparatus. Therefore, HuR upregulation in
activated T cells would be predicted to allow these cells to stabilize cytokine
mRNAs and to amplify the immune response. Additionally, we will identify in
vivo HuR targets during T cell activation into distinct functional subsets by
multiplexing using cDNA arrays. This approach has the potential to identify
novel genes involved in T cells activation, which are posttranscriptionally
regulated. In summary, HuR will be examined for RNA recognition specificity and
interactions, which govern its effects on the stability or translation of
cytokine and ERG mRNAs during T cell activation.
描述(改编自研究者摘要):本应用是
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('JACK D KEENE', 18)}}的其他基金
RNA Dynamics of Transient Macromolecular Complexes in Cancer Cells
癌细胞中瞬时大分子复合物的 RNA 动力学
- 批准号:
9079771 - 财政年份:2011
- 资助金额:
$ 30.8万 - 项目类别:
RNA Dynamics of Transient Macromolecular Complexes in Cancer Cells
癌细胞中瞬时大分子复合物的 RNA 动力学
- 批准号:
8701882 - 财政年份:2011
- 资助金额:
$ 30.8万 - 项目类别:
RNA Dynamics of Transient Macromolecular Complexes in Cancer Cells
癌细胞中瞬时大分子复合物的 RNA 动力学
- 批准号:
8309938 - 财政年份:2011
- 资助金额:
$ 30.8万 - 项目类别:
RNA Dynamics of Transient Macromolecular Complexes in Cancer Cells
癌细胞中瞬时大分子复合物的 RNA 动力学
- 批准号:
8504813 - 财政年份:2011
- 资助金额:
$ 30.8万 - 项目类别:
RNA Dynamics of Transient Macromolecular Complexes in Cancer Cells
癌细胞中瞬时大分子复合物的 RNA 动力学
- 批准号:
8147997 - 财政年份:2011
- 资助金额:
$ 30.8万 - 项目类别:
POSTTRANSCRIPTIONAL GENE REGULATION IN T CELL ACTIVATION
T 细胞激活中的转录后基因调控
- 批准号:
6194598 - 财政年份:2000
- 资助金额:
$ 30.8万 - 项目类别:
POSTTRANSCRIPTIONAL GENE REGULATION IN T CELL ACTIVATION
T 细胞激活中的转录后基因调控
- 批准号:
6510938 - 财政年份:2000
- 资助金额:
$ 30.8万 - 项目类别:
POSTTRANSCRIPTIONAL GENE REGULATION IN T CELL ACTIVATION
T 细胞激活中的转录后基因调控
- 批准号:
6744055 - 财政年份:2000
- 资助金额:
$ 30.8万 - 项目类别:
POSTTRANSCRIPTIONAL GENE REGULATION IN T CELL ACTIVATION
T 细胞激活中的转录后基因调控
- 批准号:
6374361 - 财政年份:2000
- 资助金额:
$ 30.8万 - 项目类别:
FUNCTION OF MAMMALIAN ELAV RNA BINDING PROTEINS
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6376979 - 财政年份:1999
- 资助金额:
$ 30.8万 - 项目类别:
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