| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
Spinocerebellar ataxia type 1 (SCA1) is one of nine polyglutamine diseases. Ataxin-1 (Atxn1) is a causative gene for SCA1. In order to understand functions of atxn1 complex, we set up proteome analyses. We identified and quantified proteins and constructed a pathogenic networks using system biology. However, we have not succeeded to analyze atxn1-complex. In this study, we described the interacting protein to atxn1 and functions of Atxn1-complex.
(1) VCP interacts to normal and mutant atxn1. Mutant Atxn1 finally caused the increase of DNA damege. (2) We performed a systematic in vivo screen of fly library in SCA1 fly models. Using systems biology analyses, RpA1 was located at the hub position. Atxn1 actually interacted With RpA1. (3) Mutant Atxn1 binds HMGB1. We established that complementation with HMGB1 ameliorates motor dysfunction and prolongs lifespan in SCA1 model mice. We identified mitochondrial DNA damage repair by HMGB1 as a novel molecular basis.
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