AKT-1 regulates DNA-damage-induced germline apoptosis in C. elegans.
Curr Biol
; 17(3): 286-92, 2007 Feb 06.
Article
em En
| MEDLINE
| ID: mdl-17276923
ABSTRACT
The cellular response to genotoxic stress involves the integration of multiple prosurvival and proapoptotic signals that dictate whether a cell lives or dies. In mammals, AKT/PKB regulates cell survival by modulating the activity of several apoptotic proteins, including p53. In Caenorhabditis elegans, akt-1 and akt-2 regulate development in response to environmental cues by controlling the FOXO transcription factor daf-16, but the role of these genes in regulating p53-dependent apoptosis is not known. In this study, we show that akt-1 and akt-2 negatively regulate DNA-damage-induced apoptosis in the C. elegans germline. The antiapoptotic activity of akt-1 is independent of its target gene daf-16 but dependent on cep-1/p53. Although only akt-1 regulates the apoptotic activity of cep-1, both akt-1 and akt-2 modulate the intensity of the apoptotic response independently of the transcriptional activity of CEP-1. Finally, we show that AKT-1 regulates apoptosis but not cell-cycle progression downstream of the HUS-1/MRT-2 branch of the DNA damage checkpoint.
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Caenorhabditis elegans
/
Apoptose
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Proteínas de Caenorhabditis elegans
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Proteínas Proto-Oncogênicas c-akt
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Células Germinativas
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article