The RET proto-oncogene induces apoptosis: a novel mechanism for Hirschsprung disease.
EMBO J
; 19(15): 4056-63, 2000 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-10921886
ABSTRACT
The RET (rearranged during transfection) proto-oncogene encodes a tyrosine kinase receptor involved in both multiple endocrine neoplasia type 2 (MEN 2), an inherited cancer syndrome, and Hirschsprung disease (HSCR), a developmental defect of enteric neurons. We report here that the expression of RET receptor induces apoptosis. This pro-apoptotic effect of RET is inhibited in the presence of its ligand glial cell line-derived neurotrophic factor (GDNF). Furthermore, we present evidence that RET induces apoptosis via its own cleavage by caspases, a phenomenon allowing the liberation/exposure of a pro-apoptotic domain of RET. In addition, we report that Hirschsprung-associated RET mutations impair GDNF control of RET pro-apoptotic activity. These results indicate that HSCR may result from apoptosis of RET-expressing enteric neuroblasts.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
/
Apoptose
/
Receptores Proteína Tirosina Quinases
/
Proteínas de Drosophila
/
Doença de Hirschsprung
/
Fatores de Crescimento Neural
Tipo de estudo:
Etiology_studies
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
França