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
|
リソース情報 |
ショウジョウバエ |
1782R-2 |