2000 Fiscal Year Final Research Report Summary
Identification of the factors mediating ubiquitination of inclusion body in neurodegenerative diseases
| 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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| Keywords | ubiquitination / inclusion body / neurodegenerative disease / proteolysis / Machado-Joseph Disease / polyglutamine disease |
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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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Research Products
(12 results)
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[Publications] Shirane, M., Hatakeyama, S., Hattori, K., Nakayama, K.and Nakayama, K.-i.: "Common pathway for the ubiquitination of IκBα, IκBβ, and IκBε mediated by the F-box protein FWD1."J.Biol.Chem.. 274. 28169-28174 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kitagawa, M., Hatakeyama, S., Shirane, M., Matsumoto, M., Ishida, N., Hattori, K., Nakamichi, I., Kikuchi, A., Nakayama, K.-i., and Nakayama, K.: "An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of β-catenin."EMBO J.. 18. 2401-2410 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hatakeyama, S., Kitagawa, M., Nakayama, K., Shirane, M., Matsumoto, M., Hattori, K., Higashi, H., Nakano, H., Okumura, K., Onoe, K., Good, R.A., and Nakayama, K.-i.: "Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul1/F-box protein FWD1."Proc.Natl.Acad.Sci.USA. 96. 3859-3863 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Lorick, K.L., Jensen, J.P., Fang, S.Y., Ong, A.M., Hatakeyama, S., Weissman, A.M.: "RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination."Proc.Natl.Acad.Sci.USA. 96. 11364-11369 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hattori, K., Hatakeyama, S., Shirane, M., Matsumoto, M., and Nakayama, K.-i.: "Molecular dissection of the interactions among IκBα, FWD1, and Skp1 required for ubiquitin-mediated proteolysis of IκBα."J.Biol.Chem.. 274. 29641-29647 (1999)
Description
「研究成果報告書概要(欧文)」より
