| Project/Area Number |
16390290
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
NAKAJIMA Toshihiro St. Marianna University School of Medicine, Professor, 難病治療研究センター, 教授 (90260752)
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| Co-Investigator(Kenkyū-buntansha) |
YAGISHITA Naoko St. Marianna University School of Medicine, Lecturer, 難病治療研究センター, 講師 (40367389)
山崎 聡士 聖マリアンナ医科大学, 難病治療研究センター, 講師 (30367388)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2006: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | Synoviolin / Rheumatoid arthritis / P53 / synovial cell / endoreticulum / apoptosis / ubiquitin / protein degradation / プロモーター / 発現制御 / Ets因子 / ストレス / リウマチ疾患モデル / シグナルネットワーク |
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| Research Abstract |
Synoviolin is an E3 ubiquitin ligase and is implicated in endoplasmic reticulum-associated degradation. In mammals, Synoviolin plays crucial roles in various physiological and pathological processes, including embryogenesis and the pathogenesis of arthropathy. However, little is known about the molecular mechanisms of Synoviolin in these actions. To clarify these issues, we analyzed the profile of protein expression in synoviolin-null cells. Hereby, we found that Synoviolin targets tumor suppressor gene p53 for ubiquitination. Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. Furthermore, these p53 regulatory functions of Synoviolin were irrelevant to other E3 ubiquitin ligases for p53, such as MDM2, Pirh2 and Cop1, which form autoregulatory feedback loops. Our results provide novel insights into p53 signaling mediated by Synoviolin.
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