Visit our Expo - Redox and Inflammation signaling 2012

Session XIII : Cell signaling pathways leading to regulated chromatin modifications
Poster XIII, 5
MARK/Par-1 kinases, EMK and C-TAK1 regulate localization and activity of class IIa
HDACs through hierarchical phosphorylation
Maud Martin, Nathalie Mari, Julia Von Blume, Didier Vertommen, Emily Lecomte,
Sabine Ruidant, Marie-France Heinen, Malte Bachmann, Jean-Claude Twizere, Chris
Huang, Mark H. Rider, Helen Piwnica-Worms, Thomas Seufferlein, Richard Kettmann
and Franck Dequiedt
Cellular and Molecular Biology Unit, Faculty of Agronomy, B-5030, Gembloux,
Belgium. E-mail : dequiedt.f@fsagx.ac.be
Class IIa histone deacetylases (HDACs) are found both in the cytoplasm and in the nucleus
where they repress genes involved in several developmental programs. In response to specific
signals, the repressive activity of class IIa HDACs is neutralized through their
phosphorylation on multiple N-terminal serine residues and 14-3-3 mediated nuclear
exclusion. Here, we demonstrate that class IIa HDACs are subjected to signal-independent
nuclear export that relies on their constitutive phosphorylation. We identify EMK and C-
TAK1, two members of the MARK/Par-1 family, as regulator of this process. We further
show that EMK and C-TAK1 phophorylate class IIa HDACs on one of their multiple 14-3-3
binding sites and alter their subcellular localization and repressive function. Using HDAC7 as
a paradigm, we extended these findings by demonstrating that signal-independent
phosphorylation of class IIa HDACS conforms to a hierarchical pattern in which
phosphorylation of the MARK/Par-1 site is a prerequisite for the phosphorylation of the other
14-3-3 sites. We propose that this multisite hierarchical phosphorylation by a variety of
kinases allows for sophisticated regulation of class IIa HDACs function.
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