Neural precursor cells possess multiple p53-dependent apoptotic pathways.
Cell Death Differ
; 13(10): 1727-39, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-16514420
ABSTRACT
Neural precursor cells (NPCs) are markedly sensitive to apoptotic insults. p53-Dependent transcriptional activation of proapoptotic genes has been hypothesized to regulate NPC death in response to DNA damage. Recent studies of non-NPCs have also indicated that p53 may directly interact with Bcl-2 molecules and thereby regulate death independently of transcription. The contribution of transcription-independent p53 activation in NPC death has not been characterized. In this study, we found that apoptosis caused by chemotherapeutic agents in NPCs required p53 expression and new macromolecular synthesis. In contrast, NPC death induced by staurosporine, a broad kinase inhibitor, is regulated by p53 in the absence of macromolecular synthesis. The apoptosis effector molecules Bax and Bak, Apaf-1, and caspase-9 were shown to be downstream of p53 in both pathways. These findings indicate that p53 is in a unique position to regulate at least two distinct signaling portals that activate the intrinsic apoptotic death pathway in NPCs.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Proteína Supressora de Tumor p53
/
Apoptose
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
Cell Death Differ
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos