期刊
NATURE CELL BIOLOGY
卷 8, 期 12, 页码 1415-U68出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb1510
关键词
-
类别
资金
- Telethon [GGP04168] Funding Source: Medline
The developmental protein Numb is a major determinant of binary cell fates(1-3). It is also required for the differentiation of cerebellar granule cell progenitors (GCPs)(4) at a stage of development responsive to the morphogenic glycoprotein Hedehog(5,6). Hedgehog signalling is crucial for the physiological maintenance and self-renewal of neural stem cells and its deregulation is responsible for their progression towards tumorigenesis(5,7-11). The mechanisms that inhibit this pathway during the differentiation stage are poorly understood. Here, we identify Numb as a Hedgehog-pathway inhibitor that is downregulated in early GCPs and GCP-derived cancer cells. We demonstrate that the Hedgehog transcription factor Gli1 is targeted by Numb for Itch-dependent ubiquitination, which suppresses Hedgehog signals, thus arresting growth and promoting cell differentiation. This novel Numb-dependent regulatory loop may limit the extent and duration of Hedgehog signalling during neural-progenitor differentiation, and its subversion may be a relevant event in brain tumorigenesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据