| Project/Area Number |
23590324
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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 |
General medical chemistry
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| Research Institution | Kinki University |
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Principal Investigator |
SHIRAKI Takuma 近畿大学, 生物理工学部, 准教授 (10311747)
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| Co-Investigator(Renkei-kenkyūsha) |
IGARASHI Kazuhiko 東北大学, 大学院医学系研究科, 教授 (00250738)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 転写制御 / シグナル伝達 / セロトニン / エイコサノイド / 転写活性化キネティクス / 多重レポーター遺伝子 / ポリユビキチン化 / 核外排出抑制 / 核内受容体 / 蛋白質分解 / ユビキチン |
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| Research Abstract |
According to our previous findings of endogenous ligands for PPARg, we hypothesized that extracellular signaling molecules regulate PPARg activity through not only their intracellular metabolites acting as ligands, but also intracellular signals evoked by membrane associated receptors.
To analyze the temporal and spatial regulation of PPARg activity, we developed novel reporter system, by which six independent transcriptional activities were simultaneously detected. We found that expression of phosphorylation induced stabilization of PPARg proteins by itself and blocked nuclear export of PPARg protein only in the presence of SDP-1. We also analyzed the effects of PPARg mutation identified in German obese subjects on the phoshphorylation-dependent regulation, and found that P85Q mutation blocked the effects of SDP-1. Thus, we conclude that phosphorylation signal regulates PPARg activity in the distinct mechanism from that of ligands.
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