A proteome analysis of the cadmium response in Saccharomyces cerevisiae

Cadmium is very toxic at low concentrations, but the basis for its toxicity is not clearly understood. We analyzed the proteomic response of yeast cel ls to acute cadmium stress and identified 54 induced and 43 repressed prote ins. A striking result is the strong induction of 9 enzymes of the sulfur a mino acid biosynthetic pathway. Accordingly, we observed that glutathione s ynthesis is strongly increased in response to cadmium treatment. Several pr oteins with antioxidant properties were also induced. The induction of nine proteins is dependent upon the transactivator Yap1p, consistent with the c admium hypersensitive phenotype of the YAP1-disrupted strain. Most of these proteins are also overexpressed in a strain overexpressing Yap1p, a result that correlates with the cadmium hyper-resistant phenotype of this strain. Two of these Yap1p-dependent proteins, thioredoxin and thioredoxin reducta se, play an important role in cadmium tolerance because strains lacking the corresponding genes are hypersensitive to this metal. Altogether, our data indicate that the two cellular thiol redox systems, glutathione and thiore doxin, are essential for cellular defense against cadmium.