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Updated: May 4, 2026

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
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Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

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The sirtuins promote Dishevelled-1 scaffolding of TIAM1, Rac activation and cell migration

M Saxena1, S S Dykes2, S Malyarchuk1

  • 1Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA, USA.

Oncogene
|December 24, 2013
PubMed

Insights

Sirtuin1 (SIRT1) and Sirtuin2 (SIRT2) positively regulate Rac1 activation by modulating the Dishevelled (DVL)/T-cell lymphoma invasion and metastasis 1 (TIAM1) pathway, impacting cancer cell motility.

Area of Science:

  • Cellular signaling
  • Cancer biology
  • Enzymology

Background:

  • Rac1-GTPases are crucial cellular switches for signal transduction, influenced by upstream cues like Ras oncoproteins.
  • Sirtuin1 (SIRT1) and Sirtuin2 (SIRT2) are implicated in cancer, with context-dependent roles in cell motility and tumor suppression.
  • The specific role of SIRT1 and SIRT2 in Rac1 activation remained largely uncharacterized.

Purpose of the Study:

  • To investigate the role of SIRT1 and SIRT2 in the regulation of Rac1 activation.
  • To elucidate the molecular mechanisms by which sirtuins influence Rac1 signaling pathways.
  • To determine the impact of sirtuin activity on the interaction between Dishevelled (DVL) and T-cell lymphoma invasion and metastasis 1 (TIAM1).

Main Methods:

  • Assessing Rac1-GTP levels and TIAM1 guanine nucleotide exchange factor (GEF) activity.
  • Investigating the acetylation status of TIAM1 upon transient SIRT1/SIRT2 inhibition and chronic SIRT2 knockdown.
  • Analyzing the interaction between DVL1 and TIAM1 under conditions of diminished sirtuin activity.

Main Results:

  • SIRT1 and SIRT2 were found to positively regulate Rac1-GTP levels and TIAM1 activity.
  • Inhibition or knockdown of SIRT1/SIRT2 led to increased TIAM1 acetylation.
  • Reduced sirtuin activity disrupted the interaction between DVL1 and TIAM1.
  • SIRT1 was observed to modulate Dishevelled (DVL) protein levels in cancer cells.

Conclusions:

  • SIRT1 and SIRT2 positively modulate the DVL/TIAM1/Rac axis, promoting sustained Rac pathway activation.
  • This pathway is proposed as a key mechanism by which sirtuins influence cancer cell motility.
  • The findings reveal a novel regulatory role for sirtuins in Rac1 signaling with implications for cancer research.

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