Crosstalk between ER stress and p53 pathway

ER 应激与 p53 通路之间的串扰

• 批准号: 16390290
• 负责人: NAKAJIMA Toshihiro
• 金额: $ 8.13万
• 依托单位: St. Marianna University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390290/
• 关键词: 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

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.

Synoviolin 是一种 E3 泛素连接酶，参与内质网相关降解。在哺乳动物中，Synoviolin 在各种生理和病理过程中发挥着至关重要的作用，包括胚胎发生和关节病的发病机制。然而，人们对滑膜素在这些作用中的分子机制知之甚少。为了澄清这些问题，我们分析了滑膜蛋白缺失细胞中的蛋白质表达谱。由此，我们发现Synoviolin靶向抑癌基因p53进行泛素化。 Synoviolin 在细胞质中隔离和代谢 p53，并负向调节其细胞水平和生物学功能，包括转录、细胞周期调节和凋亡。此外，Synoviolin 的这些 p53 调节功能与 p53 的其他 E3 泛素连接酶（例如 MDM2、Pirh2 和 Cop1）无关，它们形成自动调节反馈环。我们的结果为滑膜蛋白介导的 p53 信号传导提供了新的见解。

项目成果

The Nuclear Import of RNA helicase A is mediated by importin a3

RNA 解旋酶 A 的核输入由输入 a3 介导

• 发表时间: 2006
• 期刊: Biochemical and Biophysical Research Communications 340
• 作者: Satoko Aratani;et al.
• 通讯作者: et al.

Comparative Analysis of Gene Expression Profiles in Intact Versus Damaged Regions of Human Osteoarthritic Cartilage

人类骨关节炎软骨完整区域与受损区域基因表达谱的比较分析

• 发表时间: 2006
• 期刊: Arthritis and Rheumatism 54・3
• 作者: Tomoo Sato;et al.
• 通讯作者: et al.

関節リウマチの滑膜増殖機構

类风湿性关节炎滑膜增殖机制

• 发表时间: 2005
• 期刊: 日本臨床 63巻増刊5号(In press)
• 作者: 加藤 幸裕;et al.
• 通讯作者: et al.