Protein phosphatase PP1-NIPP1 activates mesenchymal genes in HeLa cells

Nele Van Dessel; Shannah Boens; Bart Lesage; Claudia Winkler; Janina Görnemann; Aleyde Van Eynde; Mathieu Bollen

doi:10.1016/j.febslet.2015.04.017

Protein phosphatase PP1-NIPP1 activates mesenchymal genes in HeLa cells

FEBS Lett. 2015 May 22;589(12):1314-21. doi: 10.1016/j.febslet.2015.04.017. Epub 2015 Apr 20.

Authors

Nele Van Dessel¹, Shannah Boens¹, Bart Lesage¹, Claudia Winkler¹, Janina Görnemann¹, Aleyde Van Eynde², Mathieu Bollen³

Affiliations

¹ Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium.
² Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium. Electronic address: [email protected].
³ Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium. Electronic address: [email protected].

PMID: 25907536
DOI: 10.1016/j.febslet.2015.04.017

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.

Keywords: HeLa cells; Mesenchymal lineage; Nuclear inhibitor of PP1; Protein phosphatase-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Biomarkers / metabolism
Cell Proliferation
Cell Transdifferentiation
Endoribonucleases / chemistry
Endoribonucleases / genetics
Endoribonucleases / metabolism*
Epithelial-Mesenchymal Transition*
Gene Expression Regulation, Neoplastic*
Genes, Neoplasm*
HeLa Cells
Humans
Ligands
Mutation
Neoplasm Proteins / chemistry
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Phosphoprotein Phosphatases / chemistry
Phosphoprotein Phosphatases / genetics
Phosphoprotein Phosphatases / metabolism*
Phosphorylation
Protein Interaction Domains and Motifs
Protein Processing, Post-Translational*
Protein Stability
RNA-Binding Proteins / chemistry
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism*
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / metabolism
Transcriptional Activation*

Substances

Biomarkers
Ligands
Neoplasm Proteins
RNA-Binding Proteins
Recombinant Fusion Proteins
Endoribonucleases
Phosphoprotein Phosphatases
PPP1R8 protein, human