Studies on regulatory mechanism for cell migration based on chemical genetics

基于化学遗传学的细胞迁移调控机制研究

• 批准号: 19310146
• 负责人: IMOTO Masaya
• 金额: $ 11.15万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19310146/
• 关键词: 遺伝子; 癌; シグナル伝達; 5-リポキシゲナーゼ; ロイコトリエンC_4; CysLT1; 遊走; ラメリポディア; Rac1; UTKO-1; 細胞遊走; ビオチン標識; Rac; フィロポディア; ピエリシジン

UTKO1 was synthesized as a derivative of moverastin by Prof. Watanabe (Univ. Tokyo). We explored the mode of action of UTKO1 by using a chemical genetic approach. We found that UTKO1 inhibited EGF-induced cell migration by inhibiting Rac1 activation. To identify the molecular target of UTKO1, biotinylated UTKO1 was synthesized by Prof. Watanabe, and was used as the probe to obtain a target protein of UTKO1. As a result, 14-3-3ζ was identified as the functional target protein of UTKO1, because siRNA-mediated silencing of 14-3-3ζ expression suppressed both EGF-induced cell migration and Rac1 activation. These results suggest that 14-3-3ζ would act upstream of Rac1 activation in the process of EGF-induced cell migration, and UTKO1 inhibited cell migration possibly due to the abrogation of 14-3-3ζ function.

UTKO 1由Watanabe教授（东京大学）合成，为莫维拉汀的衍生物。我们通过化学遗传学方法探索了UTKO 1的作用模式。我们发现UTKO 1通过抑制Rac 1的激活来抑制EGF诱导的细胞迁移。为了鉴定UTKO 1的分子靶标，Watanabe教授合成了生物素化的UTKO 1，并将其用作探针以获得UTKO 1的靶蛋白。结果，14-3-3 β被鉴定为UTKO 1的功能性靶蛋白，因为siRNA介导的14-3-3 β表达沉默抑制EGF诱导的细胞迁移和Rac 1活化。这些结果表明，在EGF诱导的细胞迁移过程中，14-3-3 β可能在Rac 1激活的上游起作用，UTKO 1抑制细胞迁移可能是由于14-3-3 β功能的废除。

项目成果

Discovery of Incednine as a Potent Modulator of the Anti-apoptotic Function of Bel-xL from Microbial Origin

发现 Incednine 作为微生物来源的 Bel-xL 抗凋亡功能的有效调节剂

• 发表时间: 2008
• 期刊: J. Am. Chem. Soc. 130
• 作者: Y. Futamura;R. Sawa;Y. Umezawa;M. Igarashi;H. Nakamura;K. Hasegawa;M. Yamasaki;E. Tashiro;Y. Takahashi;Y. Akamatsu;M. Imoto
• 通讯作者: M. Imoto

Mesenchyme cells can function to induce epithelial cell proliferation in starfish embryos.

间充质细胞可以诱导海星胚胎中的上皮细胞增殖。

• 发表时间: 2010
• 期刊: Developmental Dynamics 293
• 作者: G.Hamanaka;M.Matsumoto;M.Imoto;H.Kaneko
• 通讯作者: H.Kaneko

Transcriptional regulation of human fibroblast growth factor receptor 1 by E2F-1

• DOI: 10.1016/j.gene.2009.03.004
• 发表时间: 2009-06-01
• 期刊: GENE
• 影响因子: 3.5
• 作者: Kanai, Mai;Tashiro, Etsu;Imoto, Masaya
• 通讯作者: Imoto, Masaya

Oligomycin induced the proteasomal degradation of cyclin D1 protein

• DOI: 10.1038/ja.2009.47
• 发表时间: 2009-08-01
• 期刊: JOURNAL OF ANTIBIOTICS
• 影响因子: 3.3
• 作者: Kanai, Mai;Iba, Satoru;Imoto, Masaya
• 通讯作者: Imoto, Masaya

Studies on the Regulatory Mechanism for Cell Migration Based on Chemical Gonomics

基于化学基因组学的细胞迁移调控机制研究

• 发表时间: 2009
• 作者: Carlos;Maria Reinaruth D.;高橋睦子;岡 洋樹;高野圭;MERVIO Mika;中村 尚司;高倉 浩樹;間木重行
• 通讯作者: 間木重行