Development of the screening system for a new drug which modifies the Rho small GTP-binding protein-mediated signaling pathway

修饰Rho小GTP结合蛋白介导的信号通路的新药筛选系统的开发

• 批准号: 09557011
• 负责人: TANAKA Kazuma
• 金额: $ 6.02万
• 依托单位: HOKKAIDO UNIVERSITY (1998)Osaka University (1997)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557011/
• 关键词: Budding yeast; Small GTP-binding protein; Rho; Actin cytoskeleton; Screening system; Cell wall; スクリーニング法

The Rho small GTP-binding protein is implicated in the invasion and metastasis of the cancer cells. The yeast Saccharomyces cerevisiae also possesses the Rho signaling pathway, suggesting that S.cerevisiae can be used to search for a new drug which prevents the invasion and metastasis of the cancer cells, In this study, we have attempted to establish such a system and investigated the modes of action of Rho in yeast.Modes of action of Rho : BNI1 and BNR1 are potential targets of Rho small GTP-binding protein and interact with a variety of cytoskeletal proteins, including Elongation factor 1-alfa, SPA2, and HOF1, to regulate the cytoskeletal system.Development of the screening system : Rho and Rho-related genes in mammalian cells were expressed in yeast and it was found that the expression of these genes prevents the growth of yeast cells, indicating that these yeast cells can be used to screen out a new drug which affects the Rho-signaling pathway.

Rho 小 GTP 结合蛋白与癌细胞的侵袭和转移有关。酿酒酵母也拥有Rho信号通路，这表明酿酒酵母可以用来寻找一种阻止癌细胞侵袭和转移的新药物。在本研究中，我们试图建立这样的系统并研究Rho在酵母中的作用方式。Rho的作用方式：BNI1和BNR1是Rho小分子的潜在靶点 GTP结合蛋白并与多种细胞骨架蛋白相互作用，包括延伸因子1-alfa、SPA2和HOF1，以调节细胞骨架系统。筛选系统的开发：在酵母中表达哺乳动物细胞中的Rho和Rho相关基因，发现这些基因的表达阻止酵母细胞的生长，表明这些酵母细胞可以使用 筛选出影响Rho信号通路的新药。

项目成果

Takahashi, K., et al: "Interaction of radixin with Rho small G protein GDP/GTP exchange Protein Dbl" Oncogene. 16. 3279-3284 (1998)

Takahashi, K. 等人：“radixin 与 Rho 小 G 蛋白 GDP/GTP 交换蛋白 Dbl 的相互作用”癌基因。

Tanaka,K.: "Control of reorganization of the sctin cytoskeleton by Rho family small GTP-binding proteins in yeast." Curr.Opin.Cell Biol.10・1. 112-116 (1998)

Tanaka, K.：“酵母中 Rho 家族小 GTP 结合蛋白对 sctin 细胞骨架重组的控制。”Curr.Opin.Cell Biol.10·1（1998）。

Fujiwara, T.: "Rho1p-Bni1p-Spa2p interactions : Implication in localization of Bni1p at the bud site and regulation of the actin cytoskeleton in Saccharomyces cerevisiae." Mol.Biol.Cell. 9. 1221-1233 (1998)

Fujiwara, T.：“Rho1p-Bni1p-Spa2p 相互作用：对酿酒酵母中 Bni1p 芽位点定位和肌动蛋白细胞骨架调节的影响。”

Takahashi, K.: "Interaction of radixin with Rho small G protein GDP/GTP exchange Protein Dbl" Oncogene. 16. 3279-3284 (1998)

Takahashi, K.：“radixin 与 Rho 小 G 蛋白 GDP/GTP 交换蛋白 Dbl 的相互作用”癌基因。

Asakura, T., et al.: "Isolation and characterization of a novel actin filament-binding protein from Saccharomyces cerevisiae" Oncogene. 16. 1221-130 (1998)

Asakura, T. 等人：“来自酿酒酵母的新型肌动蛋白丝结合蛋白的分离和表征”Oncogene。