| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
PARIS is identified as a substrate of the ubiquitin ligase, parkin, a gene associated with Parkinson's disease. PARIS represses the expression of the transcriptional co-activator PGC-1α, although the mechanism that controls its repressive activity and function are largely unknown. We have shown that PARIS can be modified by SUMO and that SUMOylation of PARIS regulates its transcriptional activity. We have also shown that SUMOylation of PARIS also controls its ubiquitination. The proteasome inhibitor treatment accumulated SUMO-2/3 conjugates of PARIS. The SUMOylated PARIS was more effectively ubiquitinated than the non-SUMOylated form of PARIS. The SUMO-targeted ubiquitin ligase RNF4 promoted the ubiquitination of SUMOylated PARIS. These results suggest that RNF4-mediated ubiquitination of PARIS regulates its transcription function.
We believe the present study results may improve our understanding of the role of SUMOylation in neurodegeneration in Parkinson's disease.
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