Ubiquitin-conjugating enzyme Cdc34 mediates cadmium resistance in budding yeast through ubiquitination of the transcription factor Met4

Overexpression of the ubiquitin-conjugating enzyme Cdc34 conferred strong cadmium resistance on budding yeast. Proteasome activity, which is involved in the degradation of ubiquitinated proteins, was not essential for the acquisition of resistance to cadmium. The overexpression of Cdc34 accelerated the ubiquitination of the transcription factor Met4 and reduced expression of MET25 gene, which is a target of Met4. A MET25-disrupted strain of yeast was more resistant to cadmium than was the wild-type strain, but overexpression of Cdc34 in the MET25-disrupted cells did not affect sensitivity to cadmium. Met25 is an enzyme that catalyzes the synthesis of homocysteine from sulfide (S^2-) and O-acetylhomocysteine and we detected the increased production of S^2- upon overexpression of Cdc34. Our results suggest that overexpression of Cdc34 inactivates Met4 and interferes with expression of the MET25, with subsequent production of CdS, which has low toxicity, and, thus, a decrease in the cadmium toxicity.