This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dequiedt, F.
Right arrow Articles by Kettmann, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dequiedt, F.
Right arrow Articles by Kettmann, R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2006, p. 7086-7102, Vol. 26, No. 19
0270-7306/06/$08.00+0     doi:10.1128/MCB.00231-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

New Role for hPar-1 Kinases EMK and C-TAK1 in Regulating Localization and Activity of Class IIa Histone Deacetylases

Franck Dequiedt,1* Maud Martin,1,{dagger} Julia Von Blume,2,{dagger} Didier Vertommen,3 Emily Lecomte,1 Nathalie Mari,1 Marie-France Heinen,1 Malte Bachmann,4 Jean-Claude Twizere,1 Mei Chris Huang,5 Mark H. Rider,3 Helen Piwnica-Worms,5,6,7 Thomas Seufferlein,2 and Richard Kettmann1

Cellular and Molecular Biology Unit, Faculty of Agronomy, B-5030, Gembloux, Belgium,1 Department of Internal Medicine I, University of Ulm, 89081 Ulm, Germany,2 Hormone and Metabolic Research Unit, Université Catholique de Louvain and Christian de Duve Institute of Cellular Pathology, B-1200 Brussels, Belgium,3 Pharmazentrum Frankurt/ZAFES, Allgemeine Pharmakologie und Toxikologie, Klinikum der Johann Wolfgang Goethe-University of Frankfurt, 60590 Frankfurt, Germany,4 Department of Internal Medicine,5 Department of Cell Biology and Physiology,6 Howard Hughes Medical Institute Washington University School of Medicine, St. Louis, Missouri 631107

Received 8 February 2006/ Returned for modification 12 March 2006/ Accepted 17 July 2006

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.

* Corresponding author. Mailing address: Department of Cellular and Molecular Biology, Faculté Universitaire des Sciences Agronomiques de Gembloux, 13 Ave Marechal Juin, B-5030 Gembloux, Belgium. Phone: 32 81 622 152. Fax: 32 81 613 888. E-mail: dequiedt.f{at}fsagx.ac.be.

{dagger} M.M. and J.V.B. contributed equally to this work.

Molecular and Cellular Biology, October 2006, p. 7086-7102, Vol. 26, No. 19
0270-7306/06/$08.00+0     doi:10.1128/MCB.00231-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • McGee, S. L., van Denderen, B. J.W., Howlett, K. F., Mollica, J., Schertzer, J. D., Kemp, B. E., Hargreaves, M. (2008). AMP-Activated Protein Kinase Regulates GLUT4 Transcription by Phosphorylating Histone Deacetylase 5. Diabetes 57: 860-867 [Abstract] [Full Text]  
  • Martin, M., Potente, M., Janssens, V., Vertommen, D., Twizere, J.-C., Rider, M. H., Goris, J., Dimmeler, S., Kettmann, R., Dequiedt, F. (2008). Protein phosphatase 2A controls the activity of histone deacetylase 7 during T cell apoptosis and angiogenesis. Proc. Natl. Acad. Sci. USA 105: 4727-4732 [Abstract] [Full Text]  
  • Paroni, G., Cernotta, N., Dello Russo, C., Gallinari, P., Pallaoro, M., Foti, C., Talamo, F., Orsatti, L., Steinkuhler, C., Brancolini, C. (2008). PP2A Regulates HDAC4 Nuclear Import. Mol. Biol. Cell 19: 655-667 [Abstract] [Full Text]  
  • McKinsey, T. A. (2007). Derepression of pathological cardiac genes by members of the CaM kinase superfamily. Cardiovasc Res 73: 667-677 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»