Multisubunit protein complexes pose a challenge to the coordinated regulation of individual components. We show how the yeast transactivating factor Met4 functions as a component of the SCF(Met30) ubiquitin ligase to synchronize its own activity with cofactor assembly. Cells maintain Met4 in a dormant state by a regulatory ubiquitin chain assembled by SCF(Met30). Nutritional and heavy-metal stress block Met4 ubiquitylation resulting in Met4 activation, which induces a stress-response program including cell-cycle arrest. Met4 relies on assembly with various cofactors for promoter binding. We report here that the stability of these DNA-binding cofactors is regulated by SCF(Met30). Remarkably, the transcriptional activator Met4 functions as a substrate-specificity factor in the context of SCF(Met30/Met4) to coordinate cofactor degradation with its own activity status. Our results establish an additional layer for substrate recruitment by SCF ubiquitin ligases and provide conceptual insight into coordinated regulation of protein complexes.
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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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| Evidence ID | Analyze ID | File | Description |
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