Analysis of proteolytic mechanisms of GATA-6 as novel molecular target of chemotherapy for colorectal cancer

GATA-6作为结直肠癌化疗新分子靶点的蛋白水解机制分析

• 批准号: 24701032
• 负责人: HIRONORI Ushijima
• 金额: $ 2.41万
• 依托单位: Iwate Medical University
• 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-24701032/
• 关键词: GATA-6; 転写因子; 大腸癌; PKA; JNK; cancer; cAMP

GATA-6 is transcription factor essential for differentiation or proliferation of early embryonic cells. Recently it is reported that GATA-6 involved proliferation and surviving of gastrointestinal tumor cells. In this study, I configured the research theme, "How effective is the degradation of GATA-6 as novel molecular target of chemotherapy for colorectal cancer". Especially I focused on two issues, (1) Identification of signal transduction pathway for degradation of GATA-6, and (2) Estimation of effectiveness of degradation of GATA-6 as novel anti-tumor chemotherapy. Experiment for (1) resulted that novel kinase pathway activating JNK involved degradation of GATA-6 via nuclear export pathway. The other experiment for (2) showed that JNK activator inducing proteolysis of GATA-6 arrested the cell cycle at G2/M phase, and suppressed proliferation of colorectal cancer cells.

GATA-6是早期胚胎细胞分化或增殖所必需的转录因子。最近有报道GATA-6参与了胃肠道肿瘤细胞的增殖和存活。在这项研究中，我设定了研究主题：GATA-6的降解作为结直肠癌化疗的新分子靶点有多有效。重点研究了两个问题：(1)GATA-6降解信号转导途径的确定；(2)GATA-6作为新型抗肿瘤化疗药物降解效果的评价。实验(1)结果表明，激活JNK的新的激酶途径是通过核输出途径降解GATA-6。(2)JNK激动剂诱导GATA-6蛋白降解使细胞周期停滞于G2/M期，抑制了结直肠癌细胞的增殖。

项目成果

JNK signaling promotes proteolysis of GATA-6 and suppresses growth of colorectal cancer cells.

JNK 信号传导促进 GATA-6 的蛋白水解并抑制结直肠癌细胞的生长。

• 发表时间: 2013
• 作者: 牛島弘雅;法霊崎明子;前田正知
• 通讯作者: 前田正知

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Mechanism of anisomycin-induced nuclear export of GATA-6.

茴香霉素诱导 GATA-6 核输出的机制。

• 发表时间: 2013
• 作者: Hironori Ushijima;Kimika Endo;Masatomo Maeda
• 通讯作者: Masatomo Maeda

JNKシグナルを介したGATA-6分解機構の解析

JNK信号介导的GATA-6降解机制分析

• 发表时间: 2012
• 作者: 遠藤希美加;牛島弘雅;前田正知
• 通讯作者: 前田正知

Proteolytic mechanisms of GATA-6 facilitated by activation of JNK signaling pathway

JNK信号通路激活促进GATA-6的蛋白水解机制

• 发表时间: 2012
• 作者: Hironori Ushijima;Kimika Endo;Yuki Nakanome;Masatomo Maeda
• 通讯作者: Masatomo Maeda