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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

ERK1/2 regulates SIRT2 deacetylase activity

You Hee Choi1, Hangun Kim, Sung Ho Lee

  • 1College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea.

Biochemical and Biophysical Research Communications
|June 29, 2013
PubMed

Insights

Extracellular signal-regulated kinase (ERK)1/2 enhances SIRT2 protein levels, stability, and activity. This study reveals a novel regulatory mechanism for SIRT2 function via ERK1/2 signaling.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Signaling

Background:

  • Sirtuin 2 (SIRT2) is an NAD-dependent protein deacetylase involved in various cellular processes.
  • Post-translational modifications, including phosphorylation, can modulate SIRT2 function.
  • The specific molecular mechanisms linking SIRT2 and extracellular signal-regulated kinase (ERK)1/2 signaling remain largely unelucidated.

Purpose of the Study:

  • To investigate the potential regulation of SIRT2 by ERK1/2 signaling.
  • To determine how ERK1/2 activation impacts SIRT2 protein levels, stability, and enzymatic activity.

Main Methods:

  • Over-expression of constitutively active MEK to activate ERK.
  • Treatment with U0126, a mitogen-activated kinase kinase inhibitor.
  • Co-immunoprecipitation assays to assess protein-protein interactions.
  • Measurement of SIRT2 deacetylase activity.

Main Results:

  • ERK activation led to increased SIRT2 protein levels and enhanced stability.
  • Inhibition of ERK signaling reduced SIRT2 protein levels.
  • ERK1/2 was found to interact with SIRT2 both exogenously and endogenously.
  • SIRT2 deacetylase activity was significantly upregulated in an ERK1/2-dependent manner.

Conclusions:

  • ERK1/2 signaling plays a crucial role in regulating SIRT2.
  • ERK1/2 increases SIRT2 protein levels, enhances its stability, and upregulates its deacetylase activity.
  • This study uncovers a novel signaling pathway controlling SIRT2 function, with potential implications for cellular processes regulated by SIRT2.
Keywords:
DeacetylationERK1/2Protein levelSIRT2Stability

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