Institut de Physiologie et Biologie Cellulaires, CNRS FRE 3511, Université de Poitiers, Poitiers, France.
FEBS Lett. 2013 Sep 17;587(18):3045-51. doi: 10.1016/j.febslet.2013.07.040. Epub 2013 Jul 31.
Screening for suppressors of canthin-6-one toxicity in yeast identified Yap1, a transcription factor involved in cell response to a broad range of injuries. Although canthin-6-one did not promote a significant oxidative stress, overexpression of YAP1 gene clearly increased resistance to this drug. We demonstrated that Yap1-mediated resistance involves the plasma membrane major-facilitator-superfamily efflux pump Flr1 but not the vacuolar ATP-binding-cassette transporter Ycf1. FLR1 overexpression was sufficient to reduce sensitivity to the drug, but strictly dependent on a functional YAP1 gene.
在酵母中筛选卡亭酮毒性的抑制剂时,鉴定出 Yap1,这是一种参与细胞对广泛损伤反应的转录因子。虽然卡亭酮没有促进明显的氧化应激,但 YAP1 基因的过表达明显增加了对这种药物的抗性。我们证明 Yap1 介导的抗性涉及质膜主要促进剂超家族外排泵 Flr1,但不涉及液泡 ATP 结合盒转运蛋白 Ycf1。FLR1 的过表达足以降低对药物的敏感性,但严格依赖于功能正常的 YAP1 基因。