Recent insights into Protein Phosphatase 2A structure and regulation : The reason why PP2A is no longer considered as a lazy passive housekeeping enzyme

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (2010), 14(1), 243-252

Reversible protein phosphorylation is a major intracellular mechanism for controlling many important physiological activities. In the past, most of the attention was focused primarily on protein kinases ... [more ▼]

Reversible protein phosphorylation is a major intracellular mechanism for controlling many important physiological activities. In the past, most of the attention was focused primarily on protein kinases and on their regulation, mainly because phosphatases were then viewed as simple housekeeping enzymes. But advances in the understanding of phosphatases make now clear that protein phosphatases are dynamic and highly regulated enzymes and are as important as kinases in the regulation of cellular processes involving protein phosphorylation. Protein phosphatase 2A (PP2A) is a very abundant -it accounts for as much as 1% of total cellular protein-, ubiquitous and remarkably conserved enzyme. By dephosphorylating a plethora of cellular proteins, it is involved in the regulation of nearly all cellular activities. [less ▲]

Class IIa histone deacetylases: conducting development and differentiation.

in International Journal of Developmental Biology (2009), 53(2-3), 291-301

The emergence of specialized cell types and their organisation into organs and tissues involve the temporal modulation of many genes that are essential for coordinating the correct timing of instructive ... [more ▼]

The emergence of specialized cell types and their organisation into organs and tissues involve the temporal modulation of many genes that are essential for coordinating the correct timing of instructive signals. These transcriptional changes are orchestrated with a precision that reminds that of a classical symphony. Extracellular signals are transmitted to key integrators, which then orchestrate activation or repression of specific genes. In the last decade, class IIa HDACs have emerged as crucial regulators in various developmental and differentiation processes. This review focuses on the latest studies that have provided new insights into the biological functions of class IIa HDACs and discusses important aspects of their regulation. Elucidating cellular and molecular mechanisms by which functions of class IIa HDACs are modulated could potentially lead to new therapeutic opportunities for various diseases. [less ▲]

Protein Phosphatase 2a Controls The Activity Of Histone Deacetylase 7 During T Cell Apoptosis And Angiogenesis

in Proceedings of the National Academy of Sciences of the United States of America (2008), 105(12), 4727-4732

Protein phosphatase 2A controls the subcellular distribution and biological activity of class IIa histone deacetylases

Poster (2007)

New Role For Hpar-1 Kinases Emk And C-Tak1 In Regulating Localization And Activity Of Class Iia Histone Deacetylases

in Molecular and Cellular Biology (2006), 26(19), 7086-102

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 ... [more ▼]

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. [less ▲]

Etude de la phosphorylation du site S181 et de son importance sur la régulation de l'activité de HDAC7, une histone désacétylase de classe IIa

Master's dissertation (2006)