論文 - 詳細
| RRC ID | 33043 |
|---|---|
| 著者 | Wu JT, Lin WH, Chen WY, Huang YC, Tang CY, Ho MS, Pi H, Chien CT. |
| タイトル | CSN-mediated deneddylation differentially modulates Ci(155) proteolysis to promote Hedgehog signalling responses. |
| ジャーナル | Nat Commun |
| Abstract |
The Hedgehog (Hh) morphogen directs distinct cell responses according to its distinct signalling levels. Hh signalling stabilizes transcription factor cubitus interruptus (Ci) by prohibiting SCF(Slimb)-dependent ubiquitylation and proteolysis of Ci. How graded Hh signalling confers differential SCF(Slimb)-mediated Ci proteolysis in responding cells remains unclear. Here, we show that in COP9 signalosome (CSN) mutants, in which deneddylation of SCF(Slimb) is inactivated, Ci is destabilized in low-to-intermediate Hh signalling cells. As a consequence, expression of the low-threshold Hh target gene dpp is disrupted, highlighting the critical role of CSN deneddylation on low-to-intermediate Hh signalling response. The status of Ci phosphorylation and the level of E1 ubiquitin-activating enzyme are tightly coupled to this CSN regulation. We propose that the affinity of substrate-E3 interaction, ligase activity and E1 activity are three major determinants for substrate ubiquitylation and thereby substrate degradation in vivo. |
| 巻・号 | 2 |
| ページ | 182 |
| 公開日 | 2011-2-8 |
| DOI | 10.1038/ncomms1185 |
| PII | ncomms1185 |
| PMID | 21304511 |
| PMC | PMC3105314 |
| MeSH | Animals COP9 Signalosome Complex DNA-Binding Proteins / metabolism* Drosophila / metabolism* Drosophila Proteins / metabolism* Hedgehog Proteins / metabolism* Image Processing, Computer-Assisted Microscopy, Confocal Multiprotein Complexes / metabolism* NEDD8 Protein Peptide Hydrolases / metabolism* Phosphorylation SKP Cullin F-Box Protein Ligases / metabolism* Signal Transduction / physiology* Transcription Factors / metabolism* Ubiquitins / metabolism* Wings, Animal / growth & development Wings, Animal / metabolism |
| IF | 12.121 |
| 引用数 | 9 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | |
| 各媒体での言及数の合計 | 1 |
| 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 | |
| ショウジョウバエ | 1782R-2 |