A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE.
Mol Cell
; 5(2): 207-16, 2000 Feb.
Article
en En
| MEDLINE
| ID: mdl-10882063
The Notch1 receptor is presented at the cell membrane as a heterodimer after constitutive processing by a furin-like convertase. Ligand binding induces the proteolytic release of Notch intracellular domain by a gamma-secretase-like activity. This domain translocates to the nucleus and interacts with the DNA-binding protein CSL, resulting in transcriptional activation of target genes. Here we show that an additional processing event occurs in the extracellular part of the receptor, preceding cleavage by the gamma-secretase-like activity. Purification of the activity accounting for this cleavage in vitro shows that it is due to TACE (TNFalpha-converting enzyme), a member of the ADAM (a disintegrin and metalloprotease domain) family of metalloproteases. Furthermore, experiments carried out on TACE-/- bone marrow-derived monocytic precursor cells suggest that this metalloprotease plays a prominent role in the activation of the Notch pathway.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Metaloendopeptidasas
/
Proteínas
/
Receptores de Superficie Celular
/
Desintegrinas
/
Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2000
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Estados Unidos