Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination.
Nat Cell Biol
; 8(12): 1415-23, 2006 Dec.
Article
en En
| MEDLINE
| ID: mdl-17115028
ABSTRACT
The developmental protein Numb is a major determinant of binary cell fates. It is also required for the differentiation of cerebellar granule cell progenitors (GCPs) at a stage of development responsive to the morphogenic glycoprotein Hedehog. 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. 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.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Factores de Transcripción
/
Ubiquitinas
/
Ubiquitina-Proteína Ligasas
/
Factores de Transcripción de Tipo Kruppel
/
Proteínas Hedgehog
/
Proteínas de la Membrana
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Cell Biol
Año:
2006
Tipo del documento:
Article
País de afiliación:
Italia