Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations.
Cell Death Differ
; 20(10): 1341-9, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23787999
ABSTRACT
The activation of the Akt signalling in response to cytokine receptor signalling promotes protein synthesis, cellular growth and proliferation. To determine the role of Akt in interleukin-3 (IL-3) signalling, we generated IL-3-dependent myeloid cell lines from mice lacking Akt1, Akt2 or Akt3. Akt1 deletion resulted in accelerated apoptosis at low concentrations of IL-3. Expression of constitutively active Akt1 was sufficient to delay apoptosis in response to IL-3 withdrawal, but not sufficient to induce proliferation in the absence of IL-3. Akt1 prolonged survival of Bim- or Bad-deficient cells, but not cells lacking Puma, indicating that Akt1-dependent repression of apoptosis was in part dependent on Puma and independent of Bim or Bad. Our data show that a key role of Akt1 during IL-3 signalling is to repress p53-dependent apoptosis pathways, including transcriptional upregulation of Puma. Moreover, our data indicate that regulation of BH3-only proteins by Akt is dispensable for Akt-dependent cell survival.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citocinas
/
Apoptose
/
Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Differ
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Austrália