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