title: Structure, regulation, and pharmacological modulation of PP2A phosphatases.
abstract: Protein phosphatases of the type 2A family (PP2A) represent a major fraction of cellular Ser/Thr phosphatase activity in any given human tissue. In this review, we describe how the holoenzymic nature of PP2A and the existence of several distinct PP2A composing subunits allow for the generation of multiple structurally and functionally different PP2A complexes, explaining why PP2A is involved in the regulation of so many diverse cell biological and physiological processes. Moreover, in human disease, most notably in several cancers and Alzheimer's Disease, PP2A expression and/or activity have been found significantly decreased, underscoring its important functions as a major tumor suppressor and tau phosphatase. Hence, several recent preclinical studies have demonstrated that pharmacological restoration of PP2A activity, as well as pharmacological PP2A inhibition, under certain conditions, may be of significant future therapeutic value.
authors.affiliation: Laboratory of Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lambrecht
authors.forename: Dorien
authors.initials: D
authors.lastname: Haesen
authors.forename: Ward
authors.initials: W
authors.lastname: Sents
authors.forename: Elitsa
authors.initials: E
authors.lastname: Ivanova
authors.forename: Veerle
authors.initials: V
authors.lastname: Janssens
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism; D020536:Enzyme Activators / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D020035:Holoenzymes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D020035:Holoenzymes; D007527:Isoenzymes; D054648:Protein Phosphatase 2