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Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
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Published on: February 27, 2016

hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase

H Vaziri1, S K Dessain, E Ng Eaton

  • 1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Cell
|October 24, 2001
PubMed

Insights

The human gene hSIR2 (SIRT1) protein deacetylates and inhibits the tumor suppressor p53. This deacetylation regulates p53

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • DNA damage triggers p53 acetylation, leading to cell growth arrest or apoptosis.
  • The hSIR2 (SIRT1) protein, a human homolog of yeast Sir2, is implicated in aging and DNA damage response.

Purpose of the Study:

  • To investigate the role of hSIR2 (SIRT1) in regulating p53 protein activity.
  • To determine if hSIR2 (SIRT1) directly interacts with and modifies p53.

Main Methods:

  • Studied the interaction between hSIR2 (SIRT1) and p53 in human cells.
  • Assessed the effect of wild-type and catalytically inactive hSIR2 (SIRT1) on p53 transcriptional activity.
  • Measured p53-dependent apoptosis and radiosensitivity.

Main Results:

  • hSIR2 (SIRT1) binds to and deacetylates p53, specifically at the C-terminal Lys382 residue.
  • Expression of wild-type hSIR2 (SIRT1) reduces p53 transcriptional activity.
  • Inactive hSIR2 (SIRT1) enhances p53-dependent apoptosis and radiosensitivity.

Conclusions:

  • hSIR2 (SIRT1) negatively regulates p53 function through deacetylation.
  • SIRT1 plays a critical role in the DNA damage response pathway by modulating p53 activity.

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