Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53.
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.
Jin
Yun-Hye
YH
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea.
Kim
Yeon-Jin
YJ
Kim
Dae-Won
DW
Baek
Kwang-Hyun
KH
Kang
Bok Yun
BY
Yeo
Chang-Yeol
CY
Lee
Kwang-Youl
KY
D048948:14-3-3 Proteins / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D056565:Sirtuin 2; D037761:Sirtuins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D048948:14-3-3 Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C482982:YWHAB protein, human; D051057:Proto-Oncogene Proteins c-akt; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D037761:Sirtuins