Activation of p38 MAP kinase by DNA double-strand breaks in V(D)J recombination induces a G2/M cell cycle checkpoint.
EMBO J
; 25(4): 763-73, 2006 Feb 22.
Article
em En
| MEDLINE
| ID: mdl-16456545
ABSTRACT
Delay of cell cycle progression in response to double-strand DNA breaks (DSBs) is critical to allow time for DNA repair and prevent cellular transformation. Here, we show that the p38 mitogen-activated protein (MAP) kinase signaling pathway is activated in immature thymocytes along with TcRbeta gene V(D)J recombination. Active p38 MAP kinase promotes a G2/M cell cycle checkpoint through the phosphorylation and activation of p53 in these cells in vivo. Inactivation of p38 MAP kinase and p53 is required for DN3 thymocytes to exit the G2/M checkpoint, progress through mitosis and further differentiate. We propose that p38 MAP kinase is activated by V(D)J-mediated DSBs and induces a p53-mediated G2/M checkpoint to allow DNA repair and prevent cellular transformation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Timo
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Dano ao DNA
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Linfócitos T
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Transdução de Sinais
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Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos