title: Protein phosphatase PP1-NIPP1 activates mesenchymal genes in HeLa cells.
abstract: The deletion of the protein phosphatase-1 (PP1) regulator known as Nuclear Inhibitor of PP1 (NIPP1) is embryonic lethal during gastrulation, hinting at a key role of PP1-NIPP1 in lineage specification. Consistent with this notion we show here that a mild, stable overexpression of NIPP1 in HeLa cells caused a massive induction of genes of the mesenchymal lineage, in particular smooth/cardiac-muscle and matrix markers. This reprogramming was associated with the formation of actin-based stress fibers and retracting filopodia, and a reduced proliferation potential. The NIPP1-induced mesenchymal transition required functional substrate and PP1-binding domains, suggesting that it involves the selective dephosphorylation of substrates of PP1-NIPP1.
authors.affiliation: Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Van Dessel
authors.affiliation: Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Shannah
authors.initials: S
authors.lastname: Boens
authors.affiliation: Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Lesage
authors.affiliation: Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Claudia
authors.initials: C
authors.lastname: Winkler
authors.affiliation: Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Janina
authors.initials: J
authors.lastname: Görnemann
authors.affiliation: Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium. Electronic address: Aleyde.VanEynde@med.kuleuven.be.
authors.forename: Aleyde
authors.initials: A
authors.lastname: Van Eynde
authors.affiliation: Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium. Electronic address: Mathieu.Bollen@med.kuleuven.be.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bollen
mesh_terms: D001665:Binding Sites; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D004722:Endoribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D015415:Biomarkers; D008024:Ligands; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D004722:Endoribonucleases; D010749:Phosphoprotein Phosphatases; C097081:PPP1R8 protein, human
keywords: HeLa cells; Mesenchymal lineage; Nuclear inhibitor of PP1; Protein phosphatase-1