Toxic metals are ubiquitous in the environment and all organisms possess systems to evade toxicity and acquire tolerance. The Saccharomyces cerevisiae AP-1-like protein Yap8p (systematic name YPR199c; also known as Acr1p and Arr1p) confers arsenic tolerance by stimulating enhanced transcription of the arsenic-specific detoxification genes ACR2 and ACR3. Here, we report that Yap8p is regulated at the level of degradation. We show that Yap8p is stabilized in arsenite-exposed cells in a time- and dose-dependent manner. Yap8p degradation proceeds through the ubiquitin-proteasome pathway and is dependent on the ubiquitin-conjugating enzyme Ubc4p. Further, we show that mutants that are defective in the ubiquitin-proteasome pathway display increased Yap8p levels and elevated expression of the Yap8p gene-target ACR3. Yap8p forms homodimers in vivo but dimerization is not regulated by arsenite. Instead, arsenite-stimulated Yap8p stabilization and transcriptional activation of ACR3 requires critical cysteine residues within Yap8p. Collectively, our data is consistent with a model where Yap8p is degraded by the ubiquitin-proteasome pathway in untreated cells, whereas arsenite-exposure results in Yap8p stabilization and gene activation. In this way, regulated degradation contributes to Yap8p control.
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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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