論文 - 詳細
| RRC ID | 4181 |
|---|---|
| 著者 | Nyamsuren O, Faggionato D, Loch W, Schulze E, Baumeister R. |
| タイトル | A mutation in CHN-1/CHIP suppresses muscle degeneration in Caenorhabditis elegans. |
| ジャーナル | Dev Biol |
| Abstract |
Duchenne muscular dystrophy (DMD) is one of the most severe X-linked, inherited diseases of childhood, characterized by progressive muscle wasting and weakness as the consequence of mutations in the dystrophin gene. The protein encoded by dystrophin is a huge cytosolic protein that links the intracellular F-actin filaments to the members of the dystrophin-glycoprotein-complex (DGC). Dystrophin deficiency results in the absence or reduction of complex components that are degraded through an unknown pathway. We show here that muscle degeneration in a Caenorhabditis elegans DMD model is efficiently reduced by downregulation of chn-1, encoding the homologue of the human E3/E4 ubiquitylation enzyme CHIP. A deletion mutant of chn-1 delays the cell death of body-wall muscle cells and improves the motility of animals carrying mutations in dystrophin and MyoD. Elimination of chn-1 function in the musculature, but not in the nervous system, is sufficient for this effect, and can be phenocopied by proteasome inhibitor treatment. This suggests a critical role of CHIP/CHN-1-mediated ubiquitylation in the control of muscle wasting and degeneration and identifies a potential new drug target for the treatment of this disease. |
| 巻・号 | 312(1) |
| ページ | 193-202 |
| 公開日 | 2007-12-1 |
| DOI | 10.1016/j.ydbio.2007.09.033 |
| PII | S0012-1606(07)01371-1 |
| PMID | 17961535 |
| MeSH | Actin Cytoskeleton / metabolism Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* Cell Count Cell Movement / drug effects Cell Nucleus / drug effects Cell Nucleus / metabolism Genes, Helminth Leupeptins / pharmacology Muscle, Skeletal / cytology Muscle, Skeletal / drug effects Muscular Dystrophy, Animal / genetics* Muscular Dystrophy, Animal / pathology Mutation / genetics* Myosins / metabolism Phalloidine Ubiquitin-Protein Ligases / genetics* |
| IF | 2.896 |
| 引用数 | 17 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1380 tm395 |