1999 Fiscal Year Final Research Report Summary
Analysis on interaction between triplet repeat disease gene products and neuron-specific transcription-related factors
| Project/Area Number |
10670574
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OKAZAWA Hitoshi The university of Tokyo, Hospital Internal Medicine Assistant Professor., 医学部・附属病院, 助手 (50261996)
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| Project Period (FY) |
1998 – 1999
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| Keywords | triplet repeat diseases / polyglutamine / transcription factor / neuronal death |
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| Research Abstract |
We have cloned binding proteins to the polyglutamine tract by screening human embryonic cDNA library with yeast two-hybrid method. We obtained more than 6 clones and all of them encoded polar amino acid-rich sequences. Therefore, we suspected that polar amino acid-rich sequences can bind to the polyglutamine tract via hydrogen bond. Next, we analyzed one of the clone encoding a new gene designated as PQBP-1. This protein contains WWP domain which is participated in protein-protein interaction and polar amino acid-rich sequences composed of hepta- and di-amino acid repeats. The latter region was considered to be the binding domain to the polyglutamine tract. We showed that PQBP-1 binds to the polyglutamine of both triplet repeat disease gene products and transcription-related factors. PQBP-1 acts as a negative transcriptional regulator. It is located mainly in the nucleus. Among tissues, its expression was highest in the cortex of the cerebellum. From these observations, we are investigating the role of PQBP-1 in the pathogenesis of triplet repeat disorders.
We have also used this support for the research on the role of presenilin-1 and found that presenilin-1 modulates c-Jun homodimer function. With this grant, we also found that AP-2 beta suppresses D1A dopamine receptor gene expression.
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Research Products
(10 results)
