Regulation of the SCA3 Disease Gene and Its Protein
SCA3疾病基因及其蛋白的调控
基本信息
- 批准号:6446482
- 负责人:
- 金额:$ 2.44万
- 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:2002-06-01 至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant):
The aim of this proposal is to investigate the transcriptional and
posttranslational regulation of the disease protein causing the polyglutamine
(polygln) disease spinocerebellar ataxia type-3 (SCA3), a protein known as
ataxin-3. Polygln diseases are dominantly inherited, ultimately fatal
neurodegenerative diseases, for which there is no effective therapy. A unifying
pathological feature of polygln diseases is intracellular aggregation of the
disease protein, arguing that precise control of protein homeostasis is vital
to neuronal survival. Therefore, therapeutic strategies should include efforts
to: 1) enhance degradation of the disease protein; 2) boost the protein
surveillance machinery of the neuron; and 3) modulate disease gene expression.
Toward this goal, the specific aims are to determine the cellular pathways
controlling ataxin-3 degradation, and to define the transcriptional regulation
of the SCA3 disease gene, MJD1. Specifically, studies in aim 1 hope to
demonstrate that ataxin-3 is a normal target for proteasome and caspase
proteolysis, and determine whether the proteasomal activity is inhibited by
accumulated, mutant polygln protein. Studies in aim 2 will test the hypothesis
that the Ras/MEK pathway regulates MJD1 gene transcription. A variety of
cellular and biochemical methods will be employed to answer these questions
including metabolic pulse-chase assays, coimmunoprecipitation experiments,
immunoblots, site-directed mutagenesis, cell synchronization, and promoter
analysis. The studies proposed here will further our understanding of ataxin-3
production and degradation, perhaps leading to the development of therapies for
these currently untreatable diseases.
描述(由申请人提供):
项目成果
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{{ truncateString('SARAH J BERKE', 18)}}的其他基金
Regulation of the SCA3 Disease Gene and Its Protein
SCA3疾病基因及其蛋白的调控
- 批准号:
6622450 - 财政年份:2003
- 资助金额:
$ 2.44万 - 项目类别: