| http://purl.uniprot.org/citations/24825905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24825905 | http://www.w3.org/2000/01/rdf-schema#comment | "Trans-activation element DNA-binding protein of 43 kDa (TDP-43) characterizes insoluble protein aggregates in distinct subtypes of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43 mediates many RNA processing steps within distinct protein complexes. Here we identify novel TDP-43 protein interactors found in a yeast two-hybrid screen using an adult human brain cDNA library. We confirmed the TDP-43 interaction of seven hits by co-immunoprecipitation and assessed their co-localization in HEK293E cells. As pathological TDP-43 is ubiquitinated, we focused on the ubiquitin-conjugating enzyme UBE2E3 and the ubiquitin isopeptidase Y (UBPY). When cells were treated with proteasome inhibitor, ubiquitinated and insoluble TDP-43 species accumulated. All three UBE2E family members could enhance the ubiquitination of TDP-43, whereas catalytically inactive UBE2E3(C145S) was much less efficient. Conversely, silencing of UBE2E3 reduced TDP-43 ubiquitination. We examined 15 of the 48 known disease-associated TDP-43 mutants and found that one was excessively ubiquitinated. This strong TDP-43(K263E) ubiquitination was further enhanced by proteasomal inhibition as well as UBE2E3 expression. Conversely, UBE2E3 silencing and expression of UBPY reduced TDP-43(K263E) ubiquitination. Moreover, wild-type but not active site mutant UBPY reduced ubiquitination of TDP-43 C-terminal fragments and of a nuclear import-impaired mutant. In Drosophila melanogaster, UBPY silencing enhanced neurodegenerative TDP-43 phenotypes and the accumulation of insoluble high molecular weight TDP-43 and ubiquitin species. Thus, UBE2E3 and UBPY participate in the regulation of TDP-43 ubiquitination, solubility, and neurodegeneration."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m114.561704"xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/author | "Voigt A."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/author | "Hans F."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/author | "Fiesel F.C."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/author | "Springer W."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/author | "Geisler S."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/author | "Schulz J.B."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/author | "Kahle P.J."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/author | "Rasse T.M."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/author | "Jackel S."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/author | "Strong J.C."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/pages | "19164-19179"xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/title | "UBE2E ubiquitin-conjugating enzymes and ubiquitin isopeptidase Y regulate TDP-43 protein ubiquitination."xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://purl.uniprot.org/core/volume | "289"xsd:string |
| http://purl.uniprot.org/citations/24825905 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24825905 |
| http://purl.uniprot.org/citations/24825905 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24825905 |
| http://purl.uniprot.org/uniprot/#_A0A0B4KHJ1-mappedCitation-24825905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24825905 |
| http://purl.uniprot.org/uniprot/#_A0A0A0MSV7-mappedCitation-24825905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24825905 |
| http://purl.uniprot.org/uniprot/#_A0A0A0N0L3-mappedCitation-24825905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24825905 |
| http://purl.uniprot.org/uniprot/#_A0A0A0N0L6-mappedCitation-24825905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24825905 |
| http://purl.uniprot.org/uniprot/#_A0A0A0N0M3-mappedCitation-24825905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24825905 |