Copper ions are essential at a proper level yet toxic when present in excess. To maintain a proper intracellular level, cells must be able to sense the changes in copper ion concentrations. The yeast transcription factor Mac1p plays a critical role in the transcriptional regulation of CTR1 and CTR3, both encoding high affinity copper ion transporters. Here we report that the Mac1p binding of the copper ion-responsive elements (CuREs) in the promoters of CTR1 and CTR3 is affected by copper ions. On one hand, the Mac1p DNA binding is Cu(+) coordination-dependent, and on the other hand, exogenous Cu(+) and isoelectronic Ag(+) ions disrupt the DNA binding of Mac1p. These results suggest that the Mac1p is able to sense two different levels of copper ions. These two levels are probably the physiological and toxic copper levels in yeast cells. Furthermore, we found that Mac1p undergoes posttranslational phosphorylation modification in yeast and that the phosphorylation is required for the Mac1p to become DNA-binding active. Nonphosphorylated Mac1p is unable to bind the CTR1 promoter DNA. The data support the model of intradomain interactions and indicate further that the phosphorylation probably prevents the inhibition of DNA-binding domain activity by the activation domain of Mac1p. Taken together, these findings demonstrate that Mac1p functions critically in maintaining a proper intracellular concentration of copper ions.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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