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

Tools

Item Type:	Article
Title:	Protein phosphatase 2A controls the activity of histone deacetylase 7 during T cell apoptosis and angiogenesis
Creators Name:	Martin, M., Potente, M., Janssens, V., Vertommen, D., Twizere, J.C., Rider, M.H., Goris, J., Dimmeler, S., Kettmann, R. and Dequiedt, F.
Abstract:	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.
Keywords:	Chromatin, Shuttling, Endothelial Cells, Thymocytes, 14-3-3
Source:	Proceedings of the National Academy of Sciences of the United States of America
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Volume:	105
Number:	12
Page Range:	4727-4732
Date:	25 March 2008
Official Publication:	https://doi.org/10.1073/pnas.0708455105
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

Repository Staff Only: item control page