Functional analysis of a ligand-dependent protein degradation system

配体依赖性蛋白质降解系统的功能分析

• 批准号: 24770181
• 负责人: OKADA Maiko
• 金额: $ 3万
• 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 Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24770181/
• 关键词: タンパク分解; ユビキチン; 乳癌; エストロゲン; 細胞周期

In this study, to reveal the novel mechanism of fat-soluble ligands regulating the proper protein expression, "Ligand-dependent protein degradation system" was investigated. Estrogen focused on as a ligand, the identification and functional analysis of the degradation substrates in an estrogen signaling was performed. As a result, the mitotic key regulator was degraded through Ubiquitin-proteasome system in an estrogen-dependent manner. moreover, it was shown that estrogen accelerated transition from mitosis to G1 phase. These results suggest that estrogen is related in the mitotic regulations through promoting the degradation of mitotic reugulator at M phase.This study shows that estrogen regulates target proteins level through two pathway, the protein degradation related in M/G1 phase and well known gene expression pathway in G1/S phase, providing a new insight into the mechanism of the estrogen signaling.

本研究以脂溶性配体调控蛋白质正常表达的新机制--“配体依赖的蛋白质降解系统”为研究对象。本文以雌激素为配体，对雌激素信号通路中的降解底物进行了鉴定和功能分析。结果表明，有丝分裂关键调控因子通过泛素-蛋白酶体系统以雌激素依赖的方式降解。此外，雌激素还可加速有丝分裂向G1期的转变。 这些结果表明雌激素通过促进M期有丝分裂调节因子的降解参与有丝分裂的调控，本研究表明雌激素通过两条途径调控靶蛋白水平，即M/G1期蛋白降解途径和G1/S期基因表达途径，为雌激素信号转导机制提供了新的视角。

项目成果

A mitotic estrogen receptor complex acts as an E3 ubiquitin ligase

有丝分裂雌激素受体复合物充当 E3 泛素连接酶

• 发表时间: 2013
• 作者: 丹野悠司;渡邊嘉典;岡田麻衣子
• 通讯作者: 岡田麻衣子

A mitotic estrogen receptor alpha complex acts as an E3 ubiquitin ligase

有丝分裂雌激素受体 α 复合物充当 E3 泛素连接酶

• 发表时间: 2013
• 作者: 丹野悠司;渡邊嘉典;岡田麻衣子;Maiko Okada
• 通讯作者: Maiko Okada

聖マリアンナ医科大学大学院 医学研究科 応用分子腫瘍学

圣玛丽安娜大学医学院，医学研究生院，应用分子肿瘤学