Degradation mechanism of dystrophin short isoform, Dp71
Project/Area Number |
15K09629
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Fujimoto Takahiro 京都府立医科大学, 医学(系)研究科(研究院), 講師 (10446114)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | ジストロフィン / Dp71 / 蛋白分解 / プロテアソーム / リン酸化 / 会合蛋白 / 分子間相互作用 / 脳神経細胞 / 知的障害 / 分子機序 / モデル細胞 |
Outline of Final Research Achievements |
We investigated the posttranslational regulatory mechanisms of Dp71 expression in PC12 cells and found that the constitutive expression levels of Dp71 in PC12 cells were sensitive to proteasomal inhibition. The ectopic expression of FLAG-tagged ubiquitin revealed that Dp71 was ubiquitinated intracellularly. Interestingly, proteasomal inhibition was accompanied by a posttranslational accumulation of modified Dp71, which was restored by lambda protein phosphatase treatment in vitro, indicating that phosphorylation is responsible for the modification and affects the proteasome-dependent degradation of Dp71. Furthermore, proteasomal activity-sensitive phosphorylated Dp71 is closely associated with syntrophin, and syntrophin is also regulated by proteasomal activity in a similar way to Dp71, suggesting that the posttranslational regulatory machinery for Dp71 level is coupled with Dp71-syntrophin molecular complex. Thus, the phosphorylation-UPS regulates Dp71-associated protein complex.
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] HEK293 cells express dystrophin Dp71 with nucleus-specific localization of Dp71ab.2016
Author(s)
Nishida A, Yasuno S, Takeuchi A, Awano H, Lee T, Niba ET, Fujimoto T, Itoh K, Takeshima Y, Nishio H, Matsuo M.
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Journal Title
Histochem Cell Biol.
Volume: 146
Issue: 3
Pages: 301-309
DOI
Related Report
Peer Reviewed
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