Histone deacetylase 3 localizes to the plasma membrane and is a substrate of Src

Oncogene. 2006 Jul 27;25(32):4495-500. doi: 10.1038/sj.onc.1209473. Epub 2006 Mar 13.


Histone deacetylases (HDACs) negatively regulate gene expression by removing acetyl groups from lysine residues present in histones and other proteins. Histone deacetylase 3 is unique among the Class I family of HDACs, as it is able to shuttle between the nucleus and the cytoplasm, whereas the other family members remain in the nucleus. Histone deacetylase 3 often forms complexes with corepressor proteins that do not associate with the other Class I HDACs, and its phosphorylation correlates with increased enzymatic activity. Here we show that HDAC3 also localizes to the plasma membrane in multiple cell types. Furthermore, c-Src is shown to form a complex with HDAC3 at the plasma membrane and to use HDAC3 as a substrate for phosphorylation. Our results describe a novel localization and binding partner for the HDAC3 protein, as well as implicate c-Src in HDAC3 regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CSK Tyrosine-Protein Kinase
  • Cell Line
  • Cell Membrane / enzymology*
  • Histone Deacetylases / metabolism*
  • Humans
  • Phosphorylation
  • Protein Binding
  • Protein-Tyrosine Kinases / metabolism*
  • Substrate Specificity
  • src-Family Kinases


  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • Histone Deacetylases
  • histone deacetylase 3