Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53.
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Jin YH, Kim YJ, Kim DW, Baek KH, Kang BY, Yeo CY, Lee KY
Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53.
Biochem Biophys Res Commun. 2008 Apr 11;368(3):690-5. doi: 10.1016/j.bbrc.2008.01.114. Epub 2008 Feb 4.
- PubMed ID
- 18249187 [ View in PubMed]
- 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.