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Updated: Jul 12, 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

Function of the SIRT1 protein deacetylase in cancer

Walter Stünkel1, Bee Keow Peh, Yong Cheng Tan

  • 1S*BIO PTE Ltd, 1 Singapore Science Park II, Singapore, Singapore.

Biotechnology Journal
|September 7, 2007
PubMed

Insights

Sirtuin 1 (SIRT1) is highly expressed in colon cancer, but inhibiting its deacetylase function alone did not reduce proliferation. Novel functions beyond deacetylation may drive cancer cell survival.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Sirtuin 1 (SIRT1) deacetylates tumor suppressors like p53, linking it to cellular survival.
  • Validating SIRT1 as an anti-cancer target requires understanding its in vivo expression and function.

Purpose of the Study:

  • To investigate the in vivo expression of SIRT1 in cancer specimens.
  • To determine the role of SIRT1's deacetylase activity in cancer cell proliferation and apoptosis.
  • To evaluate the efficacy of a small molecule SIRT1 inhibitor in cancer-relevant assays.

Main Methods:

  • Immunohistochemistry on human cancer specimens and cell lines.
  • SIRT1 mRNA knockdown in p53-wild-type and -mutant cell lines.
  • Assays to assess cell proliferation, apoptosis, and inhibitor activity.

Main Results:

  • Human SIRT1 is highly expressed in cancer cell lines and colon carcinoma tissues, with significant cytosolic localization.
  • SIRT1 mRNA knockdown reduced cell proliferation and induced apoptosis independently of p53 status.
  • A small molecule SIRT1 inhibitor showed limited anti-proliferative effects despite target engagement.

Conclusions:

  • SIRT1's deacetylase function may not be sufficient to explain its role in cancer cell survival.
  • Novel, non-deacetylase functions of SIRT1, potentially linked to its cytosolic expression, may drive cancer progression.
  • Targeting SIRT1 may require strategies beyond inhibiting its catalytic activity.

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