| Project/Area Number |
11480232
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Medical Institute of Bioregulation, Kyushu University |
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Principal Investigator |
NAKAYAMA Kei-ichi Medical Institute of Bioregulation Kyushu University Professor, 生体防御医学研究所, 教授 (80291508)
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| Co-Investigator(Kenkyū-buntansha) |
HATAKEYAMA Shigetsugu Medical Institute of Bioregulation Kyushu University Assoc. Prof., 生体防御医学研究所, 助教授 (70294973)
NAKAYAMA Keiko Medical Institute of Bioregulation Kyushu University Assoc. Prof., 生体防御医学研究所, 助教授 (60294972)
KITAGAWA Masatoshi Hamamatsu Med.Univ.Professor, 医学部, 教授 (50294971)
KOMINAMI Kin-ichiro Medical Institute of Bioregulation Kyushu University Research Assoc., 生体防御医学研究所, 助手 (80304830)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2000: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1999: ¥10,100,000 (Direct Cost: ¥10,100,000)
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| Keywords | ubiquitination / inclusion body / neurodegenerative disease / proteolysis / Machado-Joseph Disease / polyglutamine disease / マシャド・ジョセフ病 / ユビキチン / VCP / UFD2a / ユビキチン鎖伸長因子(E4) |
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| Research Abstract |
It has been reported that most of inclusion bodies which are found in patients' neurons of neurodegenerative diseases are ubiquitinated. The aim of this research project is to identify the factors to mediate ubiquitination of the proteins constituting the inclusion body. As a model system, we chose Machado-Joseph disease (MJD), in which polyglutamine stretch of MJD1 protein is abnormally expanded. We found that MJD1 protein undergoes ubiquitination both in vivo and in vitro. Using the in vitro ubiquitination system as an assay for detection of ubiquitinating activity, we purified the factors required for ubiquitination of MJD1 with several column chromatography. Finally, the activity was recovered in the fraction > 1,000 kDa with gel-filtration column chromatography.
We finally identified some components of the ubiquitinating enzyme complex by amino acid sequencing, and isolated the cDNA encoding the proteins. Currently we examined the biological significance and involvement of the formation of inclusion body in neurodegenerative diseases.
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