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Updated: Jul 8, 2026
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Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
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
Summary
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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