Oncogenic role of APC/C ubiquitin ligase inhibitor, Emi1

APC/C 泛素连接酶抑制剂 Emi1 的致癌作用

• 批准号: 20689033
• 负责人: KUDO Yasusei
• 金额: $ 15.23万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 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-20689033/
• 关键词: 癌; 細胞周期; ユビキチン分解; 細胞分裂; Emil; 頭頸部扁平上皮癌; ユビキチン; APC/C; Emi1; APC; C

The abnormality of checkpoint and cell division during cell cycle is thought to be a trigger of carcinogenesis. APC/C ubiquitin ligase complex regulates the protein level of many key molecules for cell division. Emi1, an inhibitor of APC/C, inhibits APC/C activity from S phase to the beginning of M phase. In the present study, we found that APC/C inhibitor, Emi1 was frequently overexpressed in cancer cell lines and head and neck cancer cases. Moreover, we found a cancer cell line that constitutively expressed Emi1 during cell cycle progression. In this cell line, Ser310 and Thr315 of Emi1 were phosphorylated by ERK-RSK pathway and this phosphorylation inhibited ubiquitin-mediated proteolysis. Constitutive Emi1 expression inhibited APC/C activity during cell cycle progression and induced overexpression of APC/C substrates.In summary, Emi1 overexpression caused by the defects of degradation induced the constitutive inhibition of APC/C activity and was involved in abnormal regulation of cell cycle and carcinogenesis.

细胞周期中检查点和细胞分裂的异常被认为是致癌的触发因素。APC/C泛素连接酶复合物调节许多细胞分裂关键分子的蛋白水平。Emi1是APC/C的抑制剂，在S期至M期初期抑制APC/C活性。在本研究中，我们发现APC/C抑制剂Emi1在癌细胞系和头颈癌病例中经常过表达。此外，我们发现一个癌细胞系在细胞周期进程中组成性地表达Emi1。在该细胞系中，Emi1的Ser310和Thr315被ERK-RSK途径磷酸化，这种磷酸化抑制了泛素介导的蛋白水解。组成型Emi1表达在细胞周期进程中抑制APC/C活性，诱导APC/C底物过表达。综上所述，降解缺陷导致的Emi1过表达诱导了APC/C活性的组成性抑制，参与了细胞周期和癌变的异常调控。

项目成果

口腔癌におけるEmi1の過剰発現とその意義

Emi1在口腔癌中的过表达及其意义

• 发表时间: 2008
• 作者: 工藤保誠;常松貴明;大林真理子;小川郁子;北島正二朗;高田隆
• 通讯作者: 高田隆

口腔癌における Survivin と Aurora-Bの過剰発現とその意義

Survivin和Aurora-B在口腔癌中的过表达及其意义

• 发表时间: 2008
• 作者: 斉広瑩;工藤保誠;小川郁;高田隆;など
• 通讯作者: など

N-cadherin expression is correlated with metastasis of spindle cell carcinoma of head and neck region

• DOI: 10.1111/j.1600-0714.2010.00966.x
• 发表时间: 2011-01-01
• 期刊: JOURNAL OF ORAL PATHOLOGY & MEDICINE
• 影响因子: 3.3
• 作者: Nguyen, Phuong T.;Kudo, Yasusei;Takata, Takashi
• 通讯作者: Takata, Takashi

SCF^BTrcp mediates stress-induced Cdc25B ubiquitylation through cooperation of an atypical consensus sequence and PEST.

SCF^BTrcp 通过非典型共有序列和 PEST 的配合介导应激诱导的 Cdc25B 泛素化。

• 期刊: J Cell Sci in press
• 作者: Uchida;S.;Watanabe;N.;Kudo;Y.;Yoshioka;K.;Matsunaga;T.;Ishizuka;Y.;Nakagama;H.;Poon;R.Y.C.;Yamashita;K.
• 通讯作者: K.

SCF^BTrcpによるCDC25Bの分解におけるPEST配列の役割

PEST 序列在 SCF^BTrcp 降解 CDC25B 中的作用

• 发表时间: 2010
• 作者: 内田早苗;渡辺信元;工藤保誠;松永司;中釜斉;山下克美
• 通讯作者: 山下克美