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Updated: Jun 6, 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 down-regulation in HeLa can induce p53 accumulation via p38 MAPK activation-dependent p300 decrease, eventually

Yanze Li1, Haruka Matsumori, Yuji Nakayama

  • 1Division of Human Genome Science, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|November 10, 2010
PubMed

Insights

Sirtuin 2 (SIRT2) down-regulation induces cancer cell apoptosis via p53 accumulation, suggesting SIRT2 as a novel cancer therapy target. This mechanism differs from its known role in cell division regulation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Sirtuin 2 (SIRT2) is an NAD+-dependent deacetylase involved in mitotic regulation and spindle checkpoint-mediated cell death.
  • Sirtuin inhibitors are investigated as anticancer agents, primarily targeting SIRT1's role in p53 deacetylation and cell survival.

Purpose of the Study:

  • To investigate a novel, non-mitotic function of SIRT2.
  • To explore SIRT2's potential as a molecular target for cancer therapy.

Main Methods:

  • Utilized siRNA to down-regulate SIRT2 expression in cancer cell lines (e.g., HeLa) and normal cells.
  • Assessed apoptosis induction and investigated the underlying molecular mechanisms involving p53, p38 MAPK, p300, and MDM2.

Main Results:

  • SIRT2 down-regulation induced apoptosis specifically in cancer cell lines, not in normal cells.
  • Apoptosis resulted from p53 accumulation, mediated by p38 MAPK-activated degradation of p300 and subsequent MDM2 degradation.

Conclusions:

  • SIRT2 possesses a novel function distinct from its role in mitotic regulation, capable of inducing cancer cell-specific apoptosis.
  • The findings establish SIRT2 as a promising molecular target for cancer therapy, providing a mechanistic basis for its therapeutic potential.

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