J Toxicol Sci. 2009 Dec;34(6):703-8. doi: 10.2131/jts.34.703.
To elucidate the role of ribosomes in the manifestation of adriamycin toxicity, ribosome-binding proteins involved in adriamycin sensitivity were identified using budding yeast as a eukaryotic model. This revealed that adriamycin toxicity was enhanced byloss of the Egd1 or Egd2 subunits of the nascent polypeptide-associated complex(NAC). NAC is a heterodimer consisting of alpha (Egd2) and beta (Egd1 or Btt1)subunits, and is known to be involved in the translocation of nascent polypeptides into mitochondria or endoplasmic reticulum and in transcriptional activation in the nucleus. Because the loss of the Btt1 subunit had no effect on adriamycin sensitivity, the NAC conformation responsible for resistance to adriamycin appears to be the Egd1/Egd2 complex. We propose that functional NACin the ribosome is involved in resistance to adriamycin toxicity.
为了阐明核糖体在阿霉素毒性表现中的作用，使用芽殖酵母作为真核模型，鉴定了与阿霉素敏感性相关的核糖体结合蛋白。这表明，缺失新生多肽相关复合物（NAC）的 Egd1 或 Egd2 亚基会增强阿霉素的毒性。NAC 是由 alpha（Egd2）和 beta（Egd1 或 Btt1）亚基组成的异二聚体，已知其参与新生多肽向线粒体或内质网的易位以及核内转录激活。由于缺失 Btt1 亚基对阿霉素敏感性没有影响，因此，对阿霉素产生抗性的 NAC 构象似乎是 Egd1/Egd2 复合物。我们提出，核糖体中功能性的 NAC 参与了对阿霉素毒性的抗性。
