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.

滑膜蛋白是一种E3泛素连接酶，参与内质网相关降解。在哺乳动物中，滑膜小提琴在各种生理和病理过程中起着至关重要的作用，包括胚胎发育和关节病的发病机制。然而，人们对Synoviolin在这些作用中的分子机制知之甚少。为了澄清这些问题，我们分析了滑膜素无效细胞中的蛋白质表达谱。因此，我们发现滑膜蛋白靶向肿瘤抑制基因p53的泛素化。滑膜素在细胞质中螯合和代谢p53，并负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，这些p53的调节功能的滑膜蛋白是无关的其他E3泛素连接酶的p53，如MDM 2，Pirh 2和Cop1，形成自动调节反馈回路。我们的研究结果提供了新的见解p53信号介导的Synoviolin。

项目成果

The nuclear import of RNA helicase A is mediated by importin-α3

• DOI: 10.1016/j.bbrc.2005.11.161
• 发表时间: 2006-02
• 期刊: Biochemical and Biophysical Research Communications
• 影响因子: 3.1
• 作者: S. Aratani;T. Oishi;Hidetoshi Fujita;M. Nakazawa;R. Fujii;N. Imamoto;Y. Yoneda;A. Fukamizu

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.

Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'

• DOI: 10.1038/sj.emboj.7601490
• 发表时间: 2007-01-10
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Yamasaki, Satoshi;Yagishita, Naoko;Nakajima, Toshihiro
• 通讯作者: Nakajima, Toshihiro

Relevance of nuclear localization and functions of RNA helicase A.

• DOI: 10.3892/ijmm.15.4.555
• 发表时间: 2005-04
• 期刊: International journal of molecular medicine
• 影响因子: 5.4
• 作者: Hidetoshi Fujita;T. Ohshima;T. Oishi;S. Aratani;R. Fujii;A. Fukamizu;T. Nakajima

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.