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 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.
Takahashi
Tsutomu
T
Hirose
Ken-ichiro
K
Mizutani
Emi
E
Naganuma
Akira
A
D021581:Active Transport, Cell Nucleus; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D004317:Doxorubicin / Q000633:toxicity*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology; D021381:Protein Transport; D012270:Ribosomes / Q000737:chemistry / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D004718:Saccharomycetales / Q000187:drug effects* / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation
D000903:Antibiotics, Antineoplastic; D004268:DNA-Binding Proteins; C078340:EGD1 protein, S cerevisiae; C097165:EGD2 protein, S cerevisiae; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C096099:nascent-polypeptide-associated complex; C063552:transcription factor BTF3; D004317:Doxorubicin