酵母基因的功能补充由哺乳动物的多药耐药性MDR基因
M Raymond1, P Gros, M Whiteway
1National Research Council of Canada, Biotechnology Research Institute, Montreal, Quebec.
概括
癌症中的多药性耐药性 (MDR) 涉及P-糖蛋白. 这项研究表明,小鼠的mdr3基因补充了酵母STE6的删除,这表明P-糖蛋白可能会在哺乳动物中输出内源性.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 哺乳动物瘤细胞中的多药性耐药性 (MDR) 与P-糖蛋白过度表达有关,P-糖蛋白作为药物排泄.
- 酵母菌的STE6基因,MDR基因的同类基因,出口a-因子交配,其删除会损害酵母菌的交配.
- 了解P-葡萄糖蛋白的功能对于癌症治疗和细胞运输机制至关重要.
研究的目的:
- 研究哺乳动物P-糖蛋白与酵母STE6.6之间的功能性保存.
- 为了确定小鼠的mdr3基因是否可以补充酵母乳6删除菌株中的交配缺陷.
- 探索P-葡萄糖蛋白在输出内源性中的潜在作用.
主要方法:
- 使用了在a-factor出口和交配中缺陷的酵母基6删除菌株.
- 在酵母ste6删除菌株中表达了小鼠mdr3基因的补充DNA.
- 评估了补充酵母细胞中a-因素出口和交配能力的恢复.
- 引入了mdr3基因的特定突变,以评估其对补充的影响.
主要成果:
- 在酵母细胞中表达小鼠mdr3基因恢复了a因子和交配能力的出口.
- 在mdr3基因产物中的特定突变 (Ser939Phe) 取消了其补充酵母细胞删除的能力.
- 这表明在基质出口中,小鼠P-糖蛋白和酵母STE6之间存在保存的功能.
结论:
- 哺乳动物的P-糖蛋白,如小鼠的mdr3,可以在功能上替代酵母STE6在出口中.
- 这些发现表明,正常哺乳动物细胞中的P-糖蛋白可能参与内源性的跨膜输出.
- 这项研究提供了P-糖蛋白在药物耐药性之外更广泛的生理作用的见解.
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