Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53.
Biochem Biophys Res Commun
; 368(3): 690-5, 2008 Apr 11.
Article
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| MEDLINE
| ID: mdl-18249187
ABSTRACT
Sirt2 is a mammalian member of the Sirtuin family of NAD(+) (nicotinamide adenine dinucleotide)-dependent protein deacetylases. Although Sir-2.1 (a Caenorhabditis elegans Sirt2 ortholog) has been reported to interact with PAR-5/FTT-2 (a C. elegans 14-3-3 homolog), the molecular significance of the interaction between Sirt2 and 14-3-3 proteins in mammalian cell is not understood. Here, we report that Sirt2 interacts with 14-3-3 beta and gamma among various 14-3-3 isoforms, and that this interaction is strengthened by AKT. Furthermore, Sirt2 deacetylates and down-regulates the transcriptional activity of p53, and 14-3-3 beta/gamma augment deacetylation and down-regulation of the p53 transcriptional activity by Sirt2 in an AKT-dependent manner. Treatment of cells with nicotinamide, an inhibitor of Sirtuins, relieves the inhibition of p53 by Sirt2 and 14-3-3 beta/gamma. Therefore, our results suggest that the interaction between Sirt2 and 14-3-3 beta/gamma is a novel mechanism for the negative regulation of p53 beside the well-characterized Mdm2-mediated repression.
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Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Proteína p53 Supresora de Tumor
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Sirtuinas
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Proteínas 14-3-3
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Proteínas Proto-Oncogénicas c-akt
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Riñón
Límite:
Humans
Idioma:
En
Año:
2008
Tipo del documento:
Article