2007 Fiscal Year Final Research Report Summary
Search for inhibitory factor for polyglutamine protein ubioquitylation
| Project/Area Number |
18590929
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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 |
IWATA Atsushi The University of Tokyo, The University of ThkyoHospital, Assistant Professor (40401038)
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| Project Period (FY) |
2006 – 2007
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| Keywords | polyglutamine / ubiquitin / proteasome |
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| Research Abstract |
This year, we tested if any of the ubiquitin like proteins could modify polyglutamine proteins. We cloned FAT10, ubl5, FubI, Isg15 and urm1 from cDNA library and made overexpression constructs for mammalian expression. We co-expressed these constructs with polyglutamine proteins and pulled down pQ with immunoprecipitation method. Immunodetection of attached proteins revealed that FAT10 was covalently attached to pulled-down pQ proteins. This was further confirmed by pulling down pQ under denatured condition to detect FAT10 covalently bound to pQs. FAT10 is known to be homologous to ubiquitin abd known to covalently conjugated to lysine residues. We tested various amounts of FAT10 with ubiquitin co-expressed to find FAT10 affects ubiquitylation of PQ protein. By overexpressing FAT10, degradation of pQ proteins are accelerated. These data suggested that FAT10 might play and important role in pQ pathogenesis. We are now confirming the data and preparing for publication.
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