論文 - 詳細
| RRC ID | 49573 |
|---|---|
| 著者 | Uechi H, Kuranaga E, Iriki T, Takano K, Hirayama S, Miura M, Hamazaki J, Murata S. |
| タイトル | Ubiquitin-Binding Protein CG5445 Suppresses Aggregation and Cytotoxicity of Amyotrophic Lateral Sclerosis-Linked TDP-43 in Drosophila. |
| ジャーナル | Mol Cell Biol |
| Abstract |
Ubiquitin-mediated protein degradation plays essential roles in proteostasis and is involved in the pathogenesis of neurodegenerative diseases in which ubiquitin-positive aberrant proteins accumulate. However, how such aberrant proteins are processed inside cells has not been fully explored. Here, we show that the product of CG5445, a previously uncharacterized Drosophila gene, prevents the accumulation of aggregate-prone ubiquitinated proteins. We found that ubiquitin conjugates were associated with CG5445, the knockdown of which caused the accumulation of detergent-insoluble ubiquitinated proteins. Furthermore, CG5445 rescued eye degeneration caused by the amyotrophic lateral sclerosis (ALS)-linked mutant TAR DNA-binding protein of 43 kDa (TDP-43), which often forms ubiquitin-positive aggregates in cells through the capacity of CG5445 to bind to ubiquitin chains. Biochemically, CG5445 inhibited the accumulation of insoluble forms and promoted their clearance. Our results demonstrate a new possible mechanism by which cells maintain ubiquitinated aggregation-prone proteins in a soluble form to decrease their cytotoxicity until they are degraded. |
| 巻・号 | 38(3) |
| 公開日 | 2018-2-1 |
| DOI | 10.1128/MCB.00195-17 |
| PII | MCB.00195-17 |
| PMID | 29109084 |
| PMC | PMC5770533 |
| MeSH | Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Amyotrophic Lateral Sclerosis / genetics* Animals Animals, Genetically Modified DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics* Drosophila melanogaster / metabolism Eye / pathology Gene Expression Regulation Gene Knockdown Techniques Heterogeneous-Nuclear Ribonucleoprotein Group F-H / genetics Heterogeneous-Nuclear Ribonucleoprotein Group F-H / metabolism Mutation Proteasome Endopeptidase Complex / genetics Proteasome Endopeptidase Complex / metabolism Solubility Ubiquitin / metabolism Ubiquitination |
| IF | 3.611 |
| 引用数 | 4 |
| リソース情報 | |
| ショウジョウバエ | 5495R-1 5445R-4 |