The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Dysfunctional nascent polypeptide-associated complex (NAC) activity in ribosomes enhances adriamycin toxicity in budding yeast
Tsutomu TakahashiKen-ichiro HiroseEmi MizutaniAkira Naganuma
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2009 Volume 34 Issue 6 Pages 703-708


To elucidate the role ofribosomes in the manifestation of adriamycin toxicity, ribosome-bindingproteins involved in adriamycin sensitivity were identified using budding yeastas 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 α (Egd2) and β (Egd1 or Btt1)subunits, and is known to be involved in the translocation of nascentpolypeptides into mitochondria or endoplasmic reticulum and in transcriptionalactivation in the nucleus. Because the loss of the Btt1 subunit had no effecton adriamycin sensitivity, the NAC conformation responsible for resistance toadriamycin appears to be the Egd1/Egd2 complex. We propose that functional NACin the ribosome is involved in resistance to adriamycin toxicity.

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© 2009 The Japanese Society of Toxicology
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