| Project/Area Number |
12308036
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
YAMAMOTO Masayuki University of Tsukuba, Institute of Basic Medical Sciences, Professor, 基礎医学系, 教授 (50166823)
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| Co-Investigator(Kenkyū-buntansha) |
MOTOHASHI Hozumi University of Tsukuba, Institute of Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (00282351)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥43,000,000 (Direct Cost: ¥38,800,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2001: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2000: ¥24,800,000 (Direct Cost: ¥24,800,000)
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| Keywords | bZip transcription factors / gene targeting / transcription / megakaryocytes / neurodegeneration / gene regulatory network / 神経変性症 |
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| Research Abstract |
Searching for target genes regulated by bZip network.
Proplatelet formation, which is regarded as a major pathway of platelet production, is severely impaired in megakaryocytes obtained from mafG-/-::mafK+/- mutant bone marrow. In order to identify the target genes of small Mafproteins which are important for platelet production, we subtracted CDNA pool of mafG-/-::mafK+/- megakaryocytes from that of wild type megakaryocytes. CDNA clones coding cytoskeletal proteins, such as actin and tubulin, were obtained. One clone obtained from the subtraction, #325, encoded novel unknown protein. Expression level of #325 was high in megakaryocytes but low in erythoid cells. This expression profile suggested that #325 plays an important role in megakaryocytic differentiation, maturation and platelet production.
Analysis of bZip network function in neuronal cells.
MafG-/-::mafK+/- compound mice display severe motor disorder which becomes apparent at two months after birth. This sign resembled hereditary hyperekplexia in human, which is caused by functional insufficiency of glycine receptor. When we examined the expression levels of glycine reseptor subunit genes, both alpha and beta subunits were reduced. This result indicated that glycine receptor subunit genes are regulated through MARE directly or indirectly.
Effect of small Maf proteins to subcellular localization of Bach proteins.
Binding activity to MARE in the brain nuclear extract from mafG-/-::mafK+/- mice was examined by EGMSA, and we found that a shifted band comnosed of Bach/small Maf heterodimers is remarkably reduced in intensity. Interestingly, nuclear localization that Bach proteins was imuuHcu in mafG-/-::mafK;/- brain. It was concluded that small Maf proteins promote the nuclear localization of Bach, which depends on bZip structure of small Maf.
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