The yeast ubiquitin ligase SCFMet30 regulates heavy metal response
| Autor: | James L. Yen, Ning-Yuan Su, Peter K. Kaiser |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
inorganic chemicals
Saccharomyces cerevisiae Proteins Saccharomyces cerevisiae chemistry.chemical_element Autophagy-Related Proteins Cell Cycle Proteins Biology Protein Serine-Threonine Kinases Anaphase-Promoting Complex-Cyclosome Methionine Ubiquitin Skp1 Phosphorylation Cell Cycle Protein Molecular Biology S phase Adaptor Proteins Signal Transducing Cadmium SKP Cullin F-Box Protein Ligases F-Box Proteins Cell Cycle Ubiquitin-Protein Ligase Complexes Cell Biology Hydrogen Peroxide Articles Cell cycle biology.organism_classification Ubiquitin ligase Repressor Proteins Checkpoint Kinase 2 Biochemistry chemistry biology.protein Carrier Proteins Protein Binding |
| Zdroj: | Molecular biology of the cell. 16(4) |
| ISSN: | 1059-1524 |
| Popis: | Cells have developed a variety of mechanisms to respond to heavy metal exposure. Here, we show that the yeast ubiquitin ligase SCFMet30plays a central role in the response to two of the most toxic environmental heavy metal contaminants, namely, cadmium and arsenic. SCFMet30inactivates the transcription factor Met4 by proteolysis-independent polyubiquitination. Exposure of yeast cells to heavy metals led to activation of Met4 as indicated by a complete loss of ubiquitinated Met4 species. The association of Met30 with Skp1 but not with its substrate Met4 was inhibited in cells treated with cadmium. Cadmium-activated Met4 induced glutathione biosynthesis as well as genes involved in sulfuramino acid synthesis. Met4 activation was important for the cellular response to cadmium because mutations in various components of the Met4-transcription complex were hypersensitive to cadmium. In addition, cell cycle analyses revealed that cadmium induced a delay in the transition from G1to S phase of the cell cycle and slow progression through S phase. Both cadmium and arsenic induced phosphorylation of the cell cycle checkpoint protein Rad53. Genetic analyses demonstrated a complex effect of cadmium on cell cycle regulation that might be important to safeguard cellular and genetic integrity when cells are exposed to heavy metals. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|