| http://purl.uniprot.org/citations/34726688 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34726688 | http://www.w3.org/2000/01/rdf-schema#comment | "The ESCRT protein CHMP2B and the RNA-binding protein TDP-43 are both associated with ALS and FTD. The pathogenicity of CHMP2B has mainly been considered a consequence of autophagy-endolysosomal dysfunction, whereas protein inclusions containing phosphorylated TDP-43 are a pathological hallmark of ALS and FTD. Intriguingly, TDP-43 pathology has not been associated with the FTD-causing CHMP2BIntron5 mutation. In this study, we identify CHMP2B as a modifier of TDP-43-mediated neurodegeneration in a Drosophila screen. Down-regulation of CHMP2B reduces TDP-43 phosphorylation and toxicity in flies and mammalian cells. Surprisingly, although CHMP2BIntron5 causes dramatic autophagy dysfunction, disturbance of autophagy does not alter TDP-43 phosphorylation levels. Instead, we find that inhibition of CK1, but not TTBK1/2 (all of which are kinases phosphorylating TDP-43), abolishes the modifying effect of CHMP2B on TDP-43 phosphorylation. Finally, we uncover that CHMP2B modulates CK1 protein levels by negatively regulating ubiquitination and the proteasome-mediated turnover of CK1. Together, our findings propose an autophagy-independent role and mechanism of CHMP2B in regulating CK1 abundance and TDP-43 phosphorylation."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.org/dc/terms/identifier | "doi:10.1083/jcb.202103033"xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Fang Y."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Chen Y."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Deng X."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Li A."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Ni J."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Sun X."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Wang Q."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Zhang K."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Cui J."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Duan Y."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Hu R."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/author | "Yue W."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/name | "J Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/pages | "e202103033"xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/title | "CHMP2B regulates TDP-43 phosphorylation and cytotoxicity independent of autophagy via CK1."xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://purl.uniprot.org/core/volume | "221"xsd:string |
| http://purl.uniprot.org/citations/34726688 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34726688 |
| http://purl.uniprot.org/citations/34726688 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34726688 |
| http://purl.uniprot.org/uniprot/#_E1JJI5-mappedCitation-34726688 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34726688 |
| http://purl.uniprot.org/uniprot/#_O97468-mappedCitation-34726688 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34726688 |
| http://purl.uniprot.org/uniprot/#_O97469-mappedCitation-34726688 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34726688 |