Dysfunctional nascent polypeptide-associated complex (NAC) activity in ribosomes enhances adriamycin toxicity in budding yeast

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 by loss of the Egd1 or Egd2 subunits of the nascent polypeptide-associated complex (NAC). NAC is a heterodimer consisting of α (Egd2) and β (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 Bttl 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 NAC in the ribosome is involved in resistance to adriamycin toxicity.