RRC ID 3892
Author Hwang GW, Furuchi T, Naganuma A.
Title The ubiquitin-conjugating enzymes, Ubc4 and Cdc34, mediate cadmium resistance in budding yeast through different mechanisms.
Journal Life Sci.
Abstract The expression of the genes encoding the ubiquitin-conjugating enzymes, Ubc4, Ubc5, and Ubc7, has been reported to be induced by cadmium in budding yeast. In contrast, we have reported that the overexpression of Cdc34, another ubiquitin-conjugating enzyme, confers resistance to cadmium. In the present study, we examined the effects of overexpression of Ubc4, Ubc5, or Ubc7 on the sensitivity of budding yeast to cadmium. We found that yeast cells that overexpressed Ubc4, but not Ubc5 or Ubc7, showed similar cadmium resistance as yeast cells that overexpressed Cdc34. The ubiquitination levels of cellular proteins were significantly increased by overexpression of Ubc4 as well as by Cdc34. As previously reported, yeast cells overexpressing Cdc34 were resistant to cadmium even in the presence of the proteasome inhibitor MG132. However, the acquired resistance to cadmium by overexpression of Ubc4 was not observed in the presence of MG132. Cdc34 overexpression has been shown to inactivate the transcriptional activity of Met4 by accelerating its ubiquitination and to reduce expression of the MET25 gene, a target gene of Met4. Unlike Cdc34, overexpression of Ubc4 did not affect the expression of the MET25 gene. These findings suggest that the mechanism of acquired resistance to cadmium by overexpression of Ubc4 is different from that of Cdc34 and that Ubc4 confers resistance to cadmium by ubiquitination of proteins other than Met4 and accelerates the degradation of these proteins in the proteasomes.
Volume 82(23-24)
Pages 1182-5
Published 2008-6-6
DOI 10.1016/j.lfs.2008.04.002
PII S0024-3205(08)00156-2
PMID 18466927
MeSH Anaphase-Promoting Complex-Cyclosome Cadmium Chloride / toxicity* Cloning, Molecular Cysteine Proteinase Inhibitors / pharmacology Dose-Response Relationship, Drug Drug Resistance, Fungal* / genetics Environmental Pollutants / toxicity* Leupeptins / pharmacology Plasmids Saccharomyces cerevisiae / drug effects* Saccharomyces cerevisiae / enzymology Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae Proteins / biosynthesis* Ubiquitin-Conjugating Enzymes / biosynthesis* Ubiquitin-Protein Ligase Complexes / biosynthesis* beta-Galactosidase / metabolism
IF 3.234
Times Cited 6
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY
Resource
Yeast BY22828