Protein phosphatase 2A controls the activity of histone deacetylase 7 during T cell apoptosis and angiogenesis


  • M. Martin
  • M. Potente
  • V. Janssens
  • D. Vertommen
  • J.C. Twizere
  • M.H. Rider
  • J. Goris
  • S. Dimmeler
  • R. Kettmann
  • F. Dequiedt


  • Proceedings of the National Academy of Sciences of the United States of America


  • Proc Natl Acad Sci U S A 105 (12): 4727-4732


  • Class IIa histone deacetylases (HDACs) act as key transcriptional regulators in several important developmental programs. Their activities are controlled via phosphorylation-dependent nucleocytoplasmic shuttling. Phosphorylation of conserved serine residues triggers association with 14-3-3 proteins and cytoplasmic relocalization of class IIa HDACs, which leads to the derepression of their target genes. Although a lot of effort has been made toward the identification of the inactivating kinases that phosphorylate class IIa HDAC 14-3-3 motifs, the existence of an antagonistic protein phosphatase remains elusive. Here we identify PP2A as a phosphatase responsible for dephosphorylating the 14-3-3 binding sites in class IIa HDACs. Interestingly, dephosphorylation of class IIa HDACs by PP2A is prevented by competitive association of 14-3-3 proteins. Using both okadaic acid treatment and RNA interference, we demonstrate that PP2A constitutively dephosphorylates the class IIa member HDAC7 to control its biological functions as a regulator of T cell apoptosis and endothelial cell functions. This study unravels a dynamic interplay among 14-3-3s, protein kinases, and PP2A and provides a model for the regulation of class IIa HDACs.