In many fungi, transcriptional responses to alkaline pH are mediated by conserved signal transduction machinery. In the homologous system in Saccharomyces cerevisiae, the zinc-finger transcription factor Rim101 is activated under alkaline conditions to regulate transcription of target genes. The activation of Rim101 is exerted through proteolytic processing of its C-terminal inhibitory domain. Regulated processing of Rim101 requires several proteins, including the calpain-like protease Rim13/Cpl1, a putative protease scaffold Rim20, putative transmembrane proteins Rim9, and Rim21/Pal2, and Rim8/Pal3 of unknown biochemical function. To identify new regulatory components and thereby determine the order of action among the components in the pathway, we screened for suppressors of rim9Delta and rim21Delta mutations. Three identified suppressors-did4/vps2, vps24, and vps4-all belonged to "class E" vps mutants, which are commonly defective in multivesicular body sorting. These mutations suppress rim8, rim9, and rim21 but not rim13 or rim20, indicating that Rim8, Rim9, and Rim21 act upstream of Rim13 and Rim20 in the pathway. Disruption of DID4, VPS24, or VPS4, by itself, uncouples pH sensing from Rim101 processing, leading to constitutive Rim101 activation. Based on extensive epistasis analysis between pathway-activating and -inactivating mutations, a model for architecture and regulation of the Rim101 pathway is proposed.
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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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