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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Identification of radicicol as an inhibitor of in vivo Ras/Raf interaction with the yeast two-hybrid screening system
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Identification of radicicol as an inhibitor of in vivo Ras/Raf interaction with the yeast two-hybrid screening system

机译：鉴定紫杉醇为酵母Ras / Raf与酵母双杂交筛选系统的体内相互作用抑制剂

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Activation of cytoplasmic serine/threonine kinase Raf-1, an important effector of Ras, requires direct binding to Ras. The yeast two-hybrid screening system used for identification of inhibitors of Ras/Raf-1 interaction showed radicicol to be an inhibitor. Radicicol has been shown to induce morphological reversion of transformed cells. Immunoprecipitation with an anti-lias antibody revealed that the in vivo Ras/Raf-1 binding in v-Ha-ras-transformed cells was also blocked by low concentrations of radicicol (0.1 similar to 1 mu g/ml), while degradation of Raf-1 was induced at concentrations higher than 2 mu g/ml. However, in vitro binding of glutathion S-transferase-fused Ras to a maltose binding protein-fused RIP3 containing the Ras-binding domain (RBD) of Raf-1 was not inhibited by radicicol. Similar two-hybrid assays with several truncated forms of Raf-1 showed that both the conserved serine/threonine-rich domain (CR2) and the C-terminal protein kinase domain (CR3) were required for the full inhibition by radicicol. These results suggest that radicicol interacts directly or indirectly with the region except with RED of Raf-1, thereby inhibiting a conformational change of Raf-1 prerequisite for binding to Ras. [References: 35]
机译：胞质丝氨酸/苏氨酸激酶Raf-1（Ras的重要效应物）的激活需要与Ras直接结合。用于鉴定Ras / Raf-1相互作用抑制剂的酵母双杂交筛选系统显示，radicicol是一种抑制剂。 Radicicol已显示可诱导转化细胞的形态逆转。用抗lias抗体进行的免疫沉淀表明，v-Ha-ras转化细胞中的体内Ras / Raf-1结合也被低浓度的radicicol（0.1类似于1μg / ml）阻断，同时Raf降解在高于2μg/ ml的浓度下诱导-1。但是，紫杉醇并不能抑制谷胱甘肽S-转移酶融合的Ras与麦芽糖结合蛋白融合的RIP3的结合，其中RIP3含有Raf-1的Ras结合域（RBD）。类似的具有几种截短形式的Raf-1的双杂交试验表明，需要完全保留的丝氨酸/苏氨酸富集结构域（CR2）和C端蛋白激酶结构域（CR3）才能完全被radicicol抑制。这些结果表明，radicicol与除Raf-1的RED以外的区域直接或间接相互作用，从而抑制与Ras结合的前提条件的Raf-1的构象变化。 [参考：35]

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