| RRC ID |
34864
|
| 著者 |
Zhou Z, Yao X, Li S, Xiong Y, Dong X, Zhao Y, Jiang J, Zhang Q.
|
| タイトル |
Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog Signaling.
|
| ジャーナル |
Dev Cell
|
| Abstract |
Hedgehog (Hh) signaling plays essential roles in animal development and tissue homeostasis, and its misregulation causes congenital diseases and cancers. Regulation of the ubiquitin/proteasome-mediated proteolysis of Ci/Gli transcription factors is central to Hh signaling, but whether deubiquitinase is involved in this process remains unknown. Here, we show that Hh stimulates the binding of a ubiquitin-specific protease Usp7 to Ci, which positively regulates Hh signaling activity through inhibiting Ci ubiquitination and degradation mediated by both Slimb-Cul1 and Hib-Cul3 E3 ligases. Furthermore, we find that Usp7 forms a complex with GMP-synthetase (GMPS) to promote Hh pathway activity. Finally, we show that the mammalian counterpart of Usp7, HAUSP, positively regulates Hh signaling by modulating Gli ubiquitination and stability. Our findings reveal a conserved mechanism by which Ci/Gli is stabilized by a deubiquitination enzyme and identify Usp7/HUASP as a critical regulator of Hh signaling and potential therapeutic target for Hh-related cancers.
|
| 巻・号 |
34(1)
|
| ページ |
58-72
|
| 公開日 |
2015-7-6
|
| DOI |
10.1016/j.devcel.2015.05.016
|
| PII |
S1534-5807(15)00352-4
|
| PMID |
26120032
|
| PMC |
PMC4627479
|
| MeSH |
Animals
DNA-Binding Proteins / metabolism*
Drosophila Proteins / metabolism*
Drosophila melanogaster / metabolism*
Hedgehog Proteins / metabolism*
Protein Processing, Post-Translational / physiology
Signal Transduction*
Transcription Factors / metabolism*
Ubiquitin / metabolism
Ubiquitination / physiology*
|
| IF |
10.092
|
| 引用数 |
39
|
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ショウジョウバエ |
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