The proper folding of proteins is continuously challenged by intrinsic and extrinsic stresses, and the accumulation of toxic misfolded proteins is associated with many human diseases. Eukaryotic cells have evolved a complex network of protein quality control pathways to protect the proteome, and these pathways are specialized for each subcellular compartment. While many details have been elucidated for how the cytosol and endoplasmic reticulum counteract proteotoxic stress, relatively little is known about the pathways protecting the nucleus from protein misfolding. Proper maintenance of nuclear proteostasis has important implications in preserving genomic integrity, as well as for aging and disease. Here, we offer a conceptual framework for how proteostasis is maintained in this organelle. We define the particular requirements that must be considered for the nucleus to manage proteotoxic stress, summarize the known and implicated pathways of nuclear protein quality control, and identify the unresolved questions in the field.
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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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