A study on the molecular mechanisms of BRCA1-mediated cell cycle regulation from a comprehensive protein interaction analysis approach

从综合蛋白质相互作用分析方法研究BRCA1介导的细胞周期调控的分子机制

• 批准号: 20590318
• 负责人: WU Wenwen
• 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 Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590318/
• 关键词: BRCA1; HERC2; 細胞周期; 乳癌; ユビキチン化; DNA障害; 複製フォーク; Claspin; G2; Mチェックポイント; Chk1; DNA修復; BRCAI

BRCA1 complex was comprehensively analyzed through the cell cycle. HERC2 specifically interacts with BRCA1. The interaction is maximal during the S phase of the cell cycle, and rapidly diminishes as cells enter mitosis. HERC2 is an E3 ligase to target the BARD1-uncoupled BRCA1 for degradation, to regulate BRCA1 stability. Concomitantly, HERC2 contributes to pre-replicative complex (pre-RC) formation and activation by the inducible phosphorylation of MCM protein and results in regulation of origin firing and replication. HERC2 plays a role in replication fork progression and stabilization with Claspin, to be involved in the G2/M checkpoint. The study elucidated HERC2 plays critical roles in BRCA1-mediated G2/M checkpoint.

BRCA 1复合物通过细胞周期进行全面分析。HERC 2与BRCA 1相互作用。这种相互作用在细胞周期的S期达到最大，并随着细胞进入有丝分裂而迅速减弱。HERC 2是一种E3连接酶，靶向BARD 1-未偶联的BRCA 1进行降解，以调节BRCA 1的稳定性。同时，HERC 2通过MCM蛋白的可诱导磷酸化促进复制前复合物（pre-RC）的形成和活化，并导致对起点放电和复制的调节。HERC 2与Claspin一起在复制叉进展和稳定中起作用，参与G2/M检查点。该研究阐明HERC 2在BRCA 1介导的G2/M检查点中起关键作用。

项目成果

BRCA1を分解するユビキチンリガーゼの同定

鉴定降解 BRCA1 的泛素连接酶

• 发表时间: 2008
• 作者: Mimori;K.;Kataoka;A.;Yamaguchi;H.;Masuda;N.;Kosaka;Y.;Ishii;H.;Ohno;S.;Mori;M.;陌間亮一;呉文文
• 通讯作者: 呉文文

BRCA1-Associated Protein 1 Interferes with BRCA1/BARD1 RING Heterodimer Activity

• DOI: 10.1158/0008-5472.can-08-3355
• 发表时间: 2009-01-01
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Nishikawa, Hiroyuki;Wu, Wenwen;Ohta, Tomohiko
• 通讯作者: Ohta, Tomohiko

pathways by proteasome inhibitors corresponds to enhanced chemosensitivity of cells to DNA damage-inducing agents.

蛋白酶体抑制剂的途径对应于细胞对 DNA 损伤诱导剂的化学敏感性增强。

• 发表时间: 2009
• 期刊: Cancer Chemother Pharmacol. 64
• 作者: Takeshita T;Wu Wu W;Koike A;Fukuda M. Ohta T
• 通讯作者: Fukuda M. Ohta T

chemosensitivity of basal-like breast cancer based on BRCA1 dysfunction.

基于 BRCA1 功能障碍的基底样乳腺癌的化疗敏感性。

• 发表时间: 2009
• 期刊: Breast Cancer Research. 16
• 作者: Ohta T;Wu W;Koike A;Koizumi H;Fukuda M
• 通讯作者: Fukuda M

Modification of the Hepatic Mito-chondrial Proteome in Response to Ischemic Preconditioning following Ischemia-Reperfusion Injury of the Rat Liver.

大鼠肝脏缺血再灌注损伤后肝脏线粒体蛋白质组的修饰对缺血预处理的反应。

• 发表时间: 2008
• 期刊: Eur Surg Res. 40
• 作者: Oshima R;Nakano H;Katayama M;Sakurai J;Wu W;Koizumi S;Asano T;Watanabe T;Asakura T;Ohta T;Otsubo T
• 通讯作者: Otsubo T