ATM phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the DNA damage response in mice.
Cancer Cell
; 21(5): 668-679, 2012 May 15.
Article
em En
| MEDLINE
| ID: mdl-22624716
ABSTRACT
DNA damage induced by ionizing radiation activates the ATM kinase, which subsequently stabilizes and activates the p53 tumor suppressor protein. Although phosphorylation of p53 by ATM was found previously to modulate p53 levels and transcriptional activities in vivo, it does not appear to be a major regulator of p53 stability. We have utilized mice bearing altered Mdm2 alleles to demonstrate that ATM phosphorylation of Mdm2 serine 394 is required for robust p53 stabilization and activation after DNA damage. In addition, we demonstrate that dephosphorylation of Mdm2 Ser394 regulates attenuation of the p53-mediated response to DNA damage. Therefore, the phosphorylation status of Mdm2 Ser394 governs p53 protein levels and functions in cells undergoing DNA damage.
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
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Proteínas Serina-Treonina Quinases
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Proteínas de Ciclo Celular
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Proteínas Supressoras de Tumor
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Proteínas de Ligação a DNA
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Proteínas Proto-Oncogênicas c-mdm2
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article