title: Ubiquitin-conjugating enzyme Cdc34 mediates methylmercury resistance in Saccharomyces cerevisiae by increasing Whi2 degradation.
abstract: Overexpression of Cdc34, a ubiquitin-conjugating enzyme, confers methylmercury resistance on yeast cells. This suggests that degradation, by the ubiquitin-proteasome (UP) system, of proteins that enhance methylmercury toxicity might be a factor in the development of methylmercury resistance. The present study shows that yeast cells overexpressing Whi2, a protein that is ubiquitinated in cells, are highly susceptible to methylmercury, suggesting that Whi2 may enhance methylmercury toxicity. Although both Whi2 deficiency and Cdc34 overexpression individually confer methylmercury resistance on yeast cells, Whi2-deficient cells overexpressing Cdc34 showed no additive resistance to methylmercury, compared with Whi2-expressing cells that overexpress Cdc34. The intracellular level of Whi2 was significantly reduced by Cdc34 overexpression; however, this reduction was almost completely attenuated when proteasomal degradation was inhibited. These results suggest that overexpression of Cdc34 confers methylmercury resistance on yeast cells through the UP system by promoting degradation of Whi2, a methylmercury toxicity-enhancing protein.
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Gi-Wook
authors.initials: GW
authors.lastname: Hwang
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Ogiwara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Akira
authors.initials: A
authors.lastname: Naganuma
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D025141:Drug Resistance, Fungal; D008767:Methylmercury Compounds / Q000633:toxicity*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D025801:Ubiquitin / Q000502:physiology; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D008767:Methylmercury Compounds; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; C470937:Whi2 protein, S cerevisiae; C577449:CDC34 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D046988:Proteasome Endopeptidase Complex