New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and activity of class IIa histone deacetylases |
| |
Authors: | Dequiedt Franck Martin Maud Von Blume Julia Vertommen Didier Lecomte Emily Mari Nathalie Heinen Marie-France Bachmann Malte Twizere Jean-Claude Huang Mei Chris Rider Mark H Piwnica-Worms Helen Seufferlein Thomas Kettmann Richard |
| |
Institution: | Cellular and Molecular Biology Unit, Faculty of Agronomy, B-5030, Gembloux, Belgium. dequiedt.f@fsagx.ac.be |
| |
Abstract: | Class IIa histone deacetylases (HDACs) are found both in the cytoplasm and in the nucleus where they repress genes involved in several major 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 microtubule affinity-regulating kinase (MARK)/Par-1 family, as regulators of this process. We further show that EMK and C-TAK1 phosphorylate 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 extend these findings by demonstrating that signal-independent phosphorylation of the most N-terminal serine residue by the MARK/Par-1 kinases, i.e., Ser155, is a prerequisite for the phosphorylation of the nearby 14-3-3 site, Ser181. We propose that this multisite hierarchical phosphorylation by a variety of kinases allows for sophisticated regulation of class IIa HDACs function. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|