| 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
|
| リソース情報 |
| 線虫 |
tm1380
tm395 |
