Related Experiment Video

Updated: Feb 6, 2026

Quantification of Site-specific Protein Lysine Acetylation and Succinylation Stoichiometry Using Data-independent Acquisition Mass Spectrometry
12:49

Quantification of Site-specific Protein Lysine Acetylation and Succinylation Stoichiometry Using Data-independent Acquisition Mass Spectrometry

Published on: April 4, 2018

12.1K

Selective targeting of cortactin tandem repeat acetylation by human lysine deacetylases

Jan Komarek1, Miroslava Vosahlikova1, Zsofia Kutil1

  • 1Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Czech Republic.

The FEBS Journal
|February 5, 2026
PubMed

Insights

Histone deacetylase 6 (HDAC6) is the main enzyme that removes acetyl groups from cortactin (CTTN), impacting cell migration. Other enzymes like SIRT1 and SIRT2 also deacetylate CTTN, offering new insights into enzyme specificity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Lysine acetylation of cortactin (CTTN) in its tandem repeat region affects actin binding, cancer cell migration, and neuronal development.
  • The specific lysine deacetylases (KDACs) responsible for CTTN deacetylation and their precise enzymatic roles are not well understood.

Purpose of the Study:

  • To investigate the site specificity and direct enzymatic activity of human KDACs on CTTN.
  • To elucidate the mechanisms by which KDACs modulate CTTN acetylation.

Main Methods:

  • Utilized genetic code expansion to create seven site-specifically acetylated CTTN variants.
  • Employed a fully reconstituted in vitro system to assess deacetylation by various human KDACs.

Main Results:

  • Identified HDAC6, specifically its second catalytic domain (DD2), as the primary deacetylase for CTTN.
  • Demonstrated that SIRT1 and SIRT2 directly deacetylate CTTN at overlapping sites in an NAD+-dependent manner.
  • Observed negligible or weak activity of other zinc-dependent HDACs, such as HDAC8, on full-length CTTN.

Conclusions:

  • HDAC6 is the principal deacetylase for cortactin.
  • SIRT1 and SIRT2 also contribute to CTTN deacetylation through NAD+-dependent mechanisms.
  • Biochemical reconstitution is valuable for understanding complex protein acetylation and deacetylation networks and KDAC substrate preferences.
Keywords:
acetylationcortactingenetic code expansionhistone deacetylase (HDAC)sirtuinsubstrate specificity

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