論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 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 | |