TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation.
Nat Cell Biol
; 3(8): 708-14, 2001 Aug.
Article
en En
| MEDLINE
| ID: mdl-11483955
ABSTRACT
Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor that has a principal role in growth control through both its cytostatic effect on many different epithelial cell types and its ability to induce programmed cell death in a variety of other cell types. Here we have used a screen for proteins that interact physically with the cytoplasmic domain of the type II TGF-beta receptor to isolate the gene encoding Daxx - a protein associated with the Fas receptor that mediates activation of Jun amino-terminal kinase (JNK) and programmed cell death induced by Fas. The carboxy-terminal portion of Daxx functions as a dominant-negative inhibitor of TGF-beta-induced apoptosis in B-cell lymphomas, and antisense oligonucleotides to Daxx inhibit TGF-beta-induced apoptosis in mouse hepatocytes. Furthermore, Daxx is involved in mediating JNK activation by TGF-beta. Our findings associate Daxx directly with the TGF-beta apoptotic-signalling pathway, and make a biochemical connection between the receptors for TGF-beta and the apoptotic machinery.
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Colección:
01-internacional
Asunto principal:
Proteínas Nucleares
/
Proteínas Portadoras
/
División Celular
/
Factor de Crecimiento Transformador beta
/
Apoptosis
/
Receptores de Factores de Crecimiento Transformadores beta
/
Proteínas Quinasas Activadas por Mitógenos
/
Péptidos y Proteínas de Señalización Intracelular
Idioma:
En
Revista:
Nat Cell Biol
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos