| RRC ID |
51559
|
| 著者 |
Hellerschmied D, Roessler M, Lehner A, Gazda L, Stejskal K, Imre R, Mechtler K, Dammermann A, Clausen T.
|
| タイトル |
UFD-2 is an adaptor-assisted E3 ligase targeting unfolded proteins.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Muscle development requires the coordinated activities of specific protein folding and degradation factors. UFD-2, a U-box ubiquitin ligase, has been reported to play a central role in this orchestra regulating the myosin chaperone UNC-45. Here, we apply an integrative in vitro and in vivo approach to delineate the substrate-targeting mechanism of UFD-2 and elucidate its distinct mechanistic features as an E3/E4 enzyme. Using Caenorhabditis elegans as model system, we demonstrate that UFD-2 is not regulating the protein levels of UNC-45 in muscle cells, but rather shows the characteristic properties of a bona fide E3 ligase involved in protein quality control. Our data demonstrate that UFD-2 preferentially targets unfolded protein segments. Moreover, the UNC-45 chaperone can serve as an adaptor protein of UFD-2 to poly-ubiquitinate unfolded myosin, pointing to a possible role of the UFD-2/UNC-45 pair in maintaining proteostasis in muscle cells.
|
| 巻・号 |
9(1)
|
| ページ |
484
|
| 公開日 |
2018-2-2
|
| DOI |
10.1038/s41467-018-02924-7
|
| PII |
10.1038/s41467-018-02924-7
|
| PMID |
29396393
|
| PMC |
PMC5797217
|
| MeSH |
Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins / metabolism*
Molecular Chaperones / metabolism*
Muscle Cells / metabolism*
Myosins / metabolism*
Proteostasis
Ubiquitin / metabolism
Ubiquitin-Protein Ligase Complexes / metabolism*
Ubiquitin-Protein Ligases / metabolism*
Ubiquitination
Unfolded Protein Response
|
| IF |
12.121
|
| 引用数 |
7
|
| リソース情報 |
| 線虫 |
tm1380 |
