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Updated: Jul 7, 2026

Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates

Published on: February 27, 2016

Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53

Yun-Hye Jin1, Yeon-Jin Kim, Dae-Won Kim

  • 1College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea.

Biochemical and Biophysical Research Communications
|February 6, 2008
PubMed

Insights

Sirtuin 2 (Sirt2) interacts with 14-3-3 proteins to inhibit p53 activity. This novel Sirt2-14-3-3 interaction, enhanced by AKT, down-regulates p53 transcription, offering a new regulatory pathway.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Signaling

Background:

  • Sirtuins are NAD(+)-dependent deacetylases regulating cellular processes.
  • The interaction between Sirt2 and 14-3-3 proteins in mammalian cells remains unclear.
  • p53 transcriptional activity is a critical target for cellular regulation.

Purpose of the Study:

  • To investigate the interaction between mammalian Sirt2 and 14-3-3 proteins.
  • To elucidate the role of this interaction in regulating p53 transcriptional activity.
  • To identify the involvement of AKT and nicotinamide in this regulatory pathway.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • Western blotting to assess protein levels and modifications.
  • Reporter assays to measure p53 transcriptional activity.
  • Treatment with nicotinamide to inhibit Sirtuin activity.

Main Results:

  • Sirt2 interacts with 14-3-3 beta and gamma isoforms.
  • AKT strengthens the Sirt2-14-3-3 interaction.
  • Sirt2 deacetylates and down-regulates p53 transcriptional activity.
  • 14-3-3 beta/gamma augment Sirt2-mediated p53 inhibition in an AKT-dependent manner.
  • Nicotinamide treatment reverses the inhibition of p53.

Conclusions:

  • The interaction between Sirt2 and 14-3-3 beta/gamma provides a novel mechanism for negative regulation of p53.
  • This pathway represents an alternative to Mdm2-mediated repression of p53.
  • Understanding this interaction offers insights into cellular stress response and cancer biology.

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