In eukaryotic cells under nonstressed conditions, the endoplasmic reticulum (ER)-located molecular chaperone BiP is associated with an ER-membrane protein Ire1 to inhibit its self-association. While ER stress leads Ire1 to form transiently BiP-unbound clusters, which strongly evoke the unfolded protein response (UPR), here we propose an alternative activation status of Ire1. When yeast cells are physiologically ER-stressed by inositol depletion for a prolonged time, the UPR is weakly activated in a sustained manner after a transient peak of activation. During persistent stress, Ire1 foci disappear, while Ire1 continues to be self-associated. Under these conditions, Ire1 may be activated as a homo-dimer, as it shows considerable activity even when carrying the W426A mutation, which allows Ire1 to form homo-dimers but not clusters. Unlike the Ire1 clusters, the nonclustered active form seems to be associated with BiP. An Ire1 mutant not carrying the BiP-association site continued to form clusters and to be activated strongly even after long-term stress. Similar observations were obtained when cells were ER-stressed by dithiothreitol. We thus propose that upon persistent ER stress, Ire1 is weakly and continuously activated in a nonclustered form through its (re)association with BiP, which disperses the Ire1 clusters.
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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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