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

• DOI: 10.1073/pnas.0708455105
• Publication Date: 2008-03-14T01:27:12Z
• Authors: Maud Martin; Michael Potente; Veerle Janssens; Didier Vertommen; Jean-Claude Twizere; Mark H. Rider; Jozef Goris; Stefanie Dimmeler; Richard Kettmann; Franck Dequiedt
• Keywords: Dephosphorylation; Histone deacetylase 5; Histone acetyltransferase

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 class HDACs, which leads to the derepression their target genes. Although a lot effort has been made toward identification inactivating kinases that phosphorylate HDAC motifs, existence an antagonistic protein phosphatase remains elusive. Here we identify PP2A responsible for dephosphorylating binding sites HDACs. Interestingly, dephosphorylation HDACs by is prevented competitive proteins. Using both okadaic acid treatment RNA interference, demonstrate constitutively dephosphorylates member HDAC7 control its biological functions regulator T cell apoptosis endothelial functions. This study unravels dynamic interplay among 14-3-3s, kinases, provides model regulation