| Project/Area Number |
24500406
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Mie University |
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Principal Investigator |
NISHIDA Tamotsu 三重大学, 生命科学研究支援センター, 助教 (50287463)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAKIBARA Shin-ichi 早稲田大学, 人間科学学術院, 教授 (70337369)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | タンパク質翻訳後修飾 / ＳＵＭＯ化 / ユビキチン化 / パーキンソン病 / SUMO化 |
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| Outline of Final Research Achievements |
PARIS/ZNF746, a member of the family of KRAB zinc-finger proteins transcriptional factors, is recently identified as a substrate of the ubiquitin E3 ligase, parkin, a gene associated with autosomal recessive juvenile parkinsonism. PARIS represses the expression of the transcriptional co-activator, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), although the mechanism that controls its repressive activity and function are largely unknown. In this study, we show that PARIS can be modified by the small ubiquitin-related modifier (SUMO) both in vivo and in vitro. Furthermore, mutational analysis reveals that two lysine residues (K189 and K286) are the major sumoylation sites on human PARIS protein. Replacement of sumoylation site lysines with arginine decreases the repression ability of the native PGC-1αgene promoter in neuroblastoma SH-SY5Y cells. These results strongly suggest a correlation between PARIS transcriptional activity and its sumoylation.
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