title: The Basic Biology of PP2A in Hematologic Cells and Malignancies.
abstract: Reversible protein phosphorylation plays a crucial role in regulating cell signaling. In normal cells, phosphoregulation is tightly controlled by a network of protein kinases counterbalanced by several protein phosphatases. Deregulation of this delicate balance is widely recognized as a central mechanism by which cells escape external and internal self-limiting signals, eventually resulting in malignant transformation. A large fraction of hematologic malignancies is characterized by constitutive or unrestrained activation of oncogenic kinases. This is in part achieved by activating mutations, chromosomal rearrangements, or constitutive activation of upstream kinase regulators, in part by inactivation of their anti-oncogenic phosphatase counterparts. Protein phosphatase 2A (PP2A) represents a large family of cellular serine/threonine phosphatases with suspected tumor suppressive functions. In this review, we highlight our current knowledge about the complex structure and biology of these phosphatases in hematologic cells, thereby providing the rationale behind their diverse signaling functions. Eventually, this basic knowledge is a key to truly understand the tumor suppressive role of PP2A in leukemogenesis and to allow further rational development of therapeutic strategies targeting PP2A.
authors.affiliation: Laboratory of Protein Phosphorylation and Proteomics, Department Cellular and Molecular Medicine, University of Leuven , Leuven , Belgium.
authors.forename: Dorien
authors.initials: D
authors.lastname: Haesen
authors.affiliation: Laboratory of Protein Phosphorylation and Proteomics, Department Cellular and Molecular Medicine, University of Leuven , Leuven , Belgium.
authors.forename: Ward
authors.initials: W
authors.lastname: Sents
authors.affiliation: Gene Expression Unit, Department Cellular and Molecular Medicine, University of Leuven , Leuven , Belgium.
authors.forename: Katleen
authors.initials: K
authors.lastname: Lemaire
authors.affiliation: Laboratory of Protein Phosphorylation and Proteomics, Department Cellular and Molecular Medicine, University of Leuven , Leuven , Belgium.
authors.forename: Yana
authors.initials: Y
authors.lastname: Hoorne
authors.affiliation: Laboratory of Protein Phosphorylation and Proteomics, Department Cellular and Molecular Medicine, University of Leuven , Leuven , Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Janssens
keywords: PP2A; PP2A-activating drugs; inhibitor; subunit; tumor suppressor reactivation therapy