| http://purl.uniprot.org/citations/34551427 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34551427 | http://www.w3.org/2000/01/rdf-schema#comment | "C9ORF72-derived dipeptide repeat proteins have emerged as the pathogenic cause of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). However, the mechanisms underlying their expression are not fully understood. Here, we demonstrate that ZNF598, the rate-limiting factor for ribosome-associated quality control (RQC), co-translationally titrates the expression of C9ORF72-derived poly(GR) protein. A Drosophila genetic screen identified key RQC factors as potent modifiers of poly(GR)-induced neurodegeneration. ZNF598 overexpression in human neuroblastoma cells inhibited the nuclear accumulation of poly(GR) protein and decreased its cytotoxicity, whereas ZNF598 deletion had opposing effects. Poly(GR)-encoding sequences in the reporter RNAs caused translational stalling and generated ribosome-associated translation products, sharing molecular signatures with canonical RQC substrates. Furthermore, ZNF598 and listerin 1, the RQC E3 ubiquitin-protein ligase, promoted poly(GR) degradation via the ubiquitin-proteasome pathway. An ALS-relevant ZNF598R69C mutant displayed loss-of-function effects on poly(GR) expression, as well as on general RQC. Moreover, RQC function was impaired in C9-ALS patient-derived neurons, whereas lentiviral overexpression of ZNF598 lowered their poly(GR) expression and suppressed proapoptotic caspase-3 activation. Taken together, we propose that an adaptive nature of the RQC-relevant ZNF598 activity allows the co-translational surveillance to cope with the atypical expression of pathogenic poly(GR) protein, thereby acquiring a neuroprotective function in C9-ALS/FTD."xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.org/dc/terms/identifier | "doi:10.1093/nar/gkab834"xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/author | "Kim J.H."xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/author | "Lee J."xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/author | "Park H."xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/author | "Park J."xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/author | "Lee J.'"xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/author | "Lim C."xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/name | "Nucleic Acids Res"xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/pages | "11294-11311"xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/title | "ZNF598 co-translationally titrates poly(GR) protein implicated in the pathogenesis of C9ORF72-associated ALS/FTD."xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://purl.uniprot.org/core/volume | "49"xsd:string |
| http://purl.uniprot.org/citations/34551427 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34551427 |
| http://purl.uniprot.org/citations/34551427 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34551427 |
| http://purl.uniprot.org/uniprot/#_A0A0B4LEV3-mappedCitation-34551427 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34551427 |
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| http://purl.uniprot.org/uniprot/#_P15357-mappedCitation-34551427 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34551427 |
| http://purl.uniprot.org/uniprot/#_A0A0B4LGZ6-mappedCitation-34551427 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34551427 |
| http://purl.uniprot.org/uniprot/#_A0A0B4K7M9-mappedCitation-34551427 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34551427 |
| http://purl.uniprot.org/uniprot/#_A0A0B4LFZ4-mappedCitation-34551427 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34551427 |
| http://purl.uniprot.org/uniprot/#_A8JNJ2-mappedCitation-34551427 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34551427 |
| http://purl.uniprot.org/uniprot/#_A8JNX2-mappedCitation-34551427 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34551427 |
| http://purl.uniprot.org/uniprot/#_A0A4D6K506-mappedCitation-34551427 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34551427 |