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Updated: Oct 17, 2025

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
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Purification of Ubiquitinated p53 Proteins from Mammalian Cells

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Repression of p53 function by SIRT5-mediated desuccinylation at Lysine 120 in response to DNA damage

Xing Liu1,2, Fangjing Rong1,2, Jinhua Tang1,2

  • 1State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China.

Cell Death and Differentiation
|October 13, 2021
PubMed

Insights

The tumor suppressor p53

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • p53 is a critical tumor suppressor protein.
  • It maintains genome stability by regulating cell cycle arrest and apoptosis.
  • Posttranslational modifications (PTMs) are key regulators of p53 activity.

Purpose of the Study:

  • To investigate the interaction between SIRT5 and p53.
  • To identify novel PTMs of p53 and their regulatory mechanisms.
  • To elucidate the role of SIRT5 in p53-mediated cellular responses.

Main Methods:

  • Mass spectrometric analysis to identify p53 PTMs.
  • Co-immunoprecipitation to study protein interactions.
  • Analysis of double knockout mice (p53-/-Sirt5-/-) to assess in vivo function.

Main Results:

  • SIRT5 interacts with p53 and suppresses its transcriptional activity.
  • A novel PTM, succinylation at Lysine 120 (K120) of p53, was identified.
  • SIRT5 functions as a desuccinylase for p53 at K120, suppressing p53 activation.
  • DNA damage-induced apoptosis and target gene expression are dependent on p53 in p53-/-Sirt5-/- mice.

Conclusions:

  • This study identifies p53 succinylation at K120 as a novel regulatory mechanism for p53 activation.
  • SIRT5 acts as a desuccinylase targeting p53, thereby modulating its tumor suppressor function.
  • The findings reveal a new layer of p53 regulation through SIRT5-mediated desuccinylation.

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