Functional Analysis of a Novel Obesity-associated E3 Ubiquitin Ligase WWP1

新型肥胖相关 E3 泛素连接酶 WWP1 的功能分析

• 批准号: 23659207
• 负责人: HIGAMI Yoshikazu
• 金额: $ 2.58万
• 依托单位: Tokyo University of Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23659207/
• 关键词: p53; WWP1; ユビキチンリガーゼ; 脂肪細胞; 肥満症

It is well known that tumor suppressor p53 transcriptionally regulates the expression of several E3 ubiquitin ligases and the ligases post-translationally modulate p53 itself. We found that the expression of p53-targeted E3 ubiquitin ligase WWP1 was specifically up-regulated in white adipose tissue(WAT) of obese mice. An insulin administration reduced the expression of WWP1 protein in WAT in obese mice. Moreover, a knockdown for WWP1 suppressed adipocyte differentiation in 3T3-L1 preadipocyte cell line. Our findings suggest that WWP1 is a novel marker protein of obese WAT, and its expression is regulated by both p53 and insulin.

众所周知，肿瘤抑制因子p53转录调节几种E3泛素连接酶的表达，这些连接酶在翻译后调节p53自身。我们发现p53靶向E3泛素连接酶WWP1在肥胖小鼠白色脂肪组织（WAT）中特异性上调表达。胰岛素可降低肥胖小鼠WAT中WWP1蛋白的表达。此外，WWP1基因的敲低抑制了3T3-L1前脂肪细胞系中脂肪细胞的分化。我们的研究结果表明，WWP1是肥胖型WAT的一种新的标记蛋白，其表达受p53和胰岛素的共同调控。