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DOI | 10.1038/ncomms14856 |
USP7 inhibits Wnt/beta-catenin signaling through promoting stabilization of Axin | |
Ji, Lei1; Lu, Bo1; Zamponi, Raffaella1,3; Charlat, Olga1; Aversa, Robert1; Yang, Zinger1; Sigoillot, Frederic1; Zhu, Xiaoping1; Hu, Tiancen1; Reece-Hoyes, John S.1; Russ, Carsten1; Michaud, Gregory1; Tchorz, Jan S.2; Jiang, Xiaomo1; Cong, Feng1 | |
2019-09-13 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Switzerland; Italy |
英文摘要 | Axin is a key scaffolding protein responsible for the formation of the beta-catenin destruction complex. Stability of Axin protein is regulated by the ubiquitin-proteasome system, and modulation of cellular concentration of Axin protein has a profound effect on Wnt/beta-catenin signaling. Although E3s promoting Axin ubiquitination have been identified, the deubiquitinase responsible for Axin deubiquitination and stabilization remains unknown. Here, we identify USP7 as a potent negative regulator of Wnt/beta-catenin signaling through CRISPR screens. Genetic ablation or pharmacological inhibition of USP7 robustly increases Wnt/beta-catenin signaling in multiple cellular systems. USP7 directly interacts with Axin through its TRAF domain, and promotes deubiquitination and stabilization of Axin. Inhibition of USP7 regulates osteoblast differentiation and adipocyte differentiation through increasing Wnt/beta-catenin signaling. Our study reveals a critical mechanism that prevents excessive degradation of Axin and identifies USP7 as a target for sensitizing cells to Wnt/beta-catenin signaling. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000485685900023 |
WOS关键词 | SMALL-MOLECULE INHIBITOR ; BETA-CATENIN ; DEUBIQUITINATING ENZYME ; CRYSTAL-STRUCTURE ; WNT ; HAUSP ; P53 ; SUBSTRATE ; ADIPOGENESIS ; RECOGNITION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203267 |
专题 | 资源环境科学 |
作者单位 | 1.Novartis Pharma AG, Novartis Inst Biomed Res, Cambridge, MA 02139 USA; 2.Novartis Pharma AG, Novartis Inst Biomed Res, Basel, Switzerland; 3.Azienda USL IRCCS Reggio Emilia, Viale Risorgimento 80, I-42123 Reggio Emila, Italy |
推荐引用方式 GB/T 7714 | Ji, Lei,Lu, Bo,Zamponi, Raffaella,et al. USP7 inhibits Wnt/beta-catenin signaling through promoting stabilization of Axin[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Ji, Lei.,Lu, Bo.,Zamponi, Raffaella.,Charlat, Olga.,Aversa, Robert.,...&Cong, Feng.(2019).USP7 inhibits Wnt/beta-catenin signaling through promoting stabilization of Axin.NATURE COMMUNICATIONS,10. |
MLA | Ji, Lei,et al."USP7 inhibits Wnt/beta-catenin signaling through promoting stabilization of Axin".NATURE COMMUNICATIONS 10(2019). |
条目包含的文件 | 条目无相关文件。 |
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