title: Cadmium inhibits the protein degradation of Sml1 by inhibiting the phosphorylation of Sml1 in Saccharomyces cerevisiae.
abstract: Cadmium is a toxic metal, and the mechanism of cadmium toxicity in living organisms has been well studied. Here, we used Saccharomyces cerevisiae as a model system to examine the detailed molecular mechanism of cell growth defects caused by cadmium. Using a plate assay of a yeast deletion mutant collection, we found that deletion of SML1, which encodes an inhibitor of Rnr1, resulted in cadmium resistance. Sml1 protein levels increased when cells were treated with cadmium, even though the mRNA levels of SML1 remained unchanged. Using northern and western blot analyses, we found that cadmium inhibited Sml1 degradation by inhibiting Sml1 phosphorylation. Sml1 protein levels increased when cells were treated with cadmium due to disruption of the dependent protein degradation pathway. Furthermore, cadmium promoted cell cycle progression into the G2 phase. The same result was obtained using cells in which SML1 was overexpressed. Deletion of SML1 delayed cell cycle progression. These results are consistent with Sml1 accumulation and with growth defects caused by cadmium stress. Interestingly, although cadmium treatment led to increase Sml1 levels, intracellular dNTP levels also increased because of Rnr3 upregulation due to cadmium stress. Taken together, these results suggest that cadmium specifically affects the phosphorylation of Sml1 and that Sml1 accumulates in cells.
authors: School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea.
authors: In-Joon
authors: IJ
authors: Baek
authors: Hyun-Jun
authors: HJ
authors: Kang
authors: Miwha
authors: M
authors: Chang
authors: Il-Dong
authors: ID
authors: Choi
authors: Chang-Min
authors: CM
authors: Kang
authors: Cheol-Won
authors: CW
authors: Yun
mesh_terms: D002104:Cadmium / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage; D010766:Phosphorylation / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D015854:Up-Regulation
chemical_list: C115052:SML1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D002104:Cadmium; D012264:Ribonucleotide Reductases; C551024:Rnr1 protein, S cerevisiae