title: The protein phosphatase-1 (PP1) regulator, nuclear inhibitor of PP1 (NIPP1), interacts with the polycomb group protein, embryonic ectoderm development (EED), and functions as a transcriptional repressor.
abstract: The nuclear protein NIPP1 (nuclear inhibitor of protein Ser/Thr phosphatase-1) interacts with the splicing factors SAP155 and CDC5L and is involved in a late step of spliceosome assembly. In addition, NIPP1 is an interactor of protein phosphatase-1 and a COOH-terminal NIPP1 fragment displays an RNase E like endoribonuclease activity. A yeast two-hybrid screening resulted in the identification of the Polycomb group protein EED (embryonic ectoderm development), an established transcriptional repressor, as a novel NIPP1 interactor. NIPP1 only interacted with full-length EED, whereas two EED interaction domains were mapped to the central and COOH-terminal thirds of NIPP1. The NIPP1-EED interaction was potentiated by the binding of (d)G-rich nucleic acids to the central domain of NIPP1. Nucleic acids also decreased the potency of NIPP1 as an inhibitor of PP1, but they did not prevent the formation of a ternary NIPP1.EED.PP1 complex. EED had no effect on the function of NIPP1 as a splicing factor or as an endoribonuclease. However, similar to EED, NIPP1 acted as a transcriptional repressor of targeted genes and this NIPP1 effect was mediated by the EED interaction domain. Also, the histone deacetylase 2 was present in a complex with NIPP1. Our data are in accordance with a role for NIPP1 as a DNA-targeting protein for EED and associated chromatin-modifying enzymes.
authors.affiliation: Division of Biochemistry, Faculty of Medicine, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Jin
authors.forename: Aleyde
authors.initials: A
authors.lastname: van Eynde
authors.forename: Monique
authors.initials: M
authors.lastname: Beullens
authors.forename: Nivedita
authors.initials: N
authors.lastname: Roy
authors.forename: Gerald
authors.initials: G
authors.lastname: Thiel
authors.forename: Willy
authors.initials: W
authors.lastname: Stalmans
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bollen
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D011232:Chemical Precipitation; D004722:Endoribonucleases / Q000378:metabolism; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2; D054645:Protein Phosphatase 1; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins; D011817:Rabbits; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism; D013489:Suppression, Genetic; D014158:Transcription, Genetic / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D015003:Yeasts
chemical_list: D002352:Carrier Proteins; C491488:EED protein, human; C107275:Eed protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C021042:protein phosphatase inhibitor-1; D012313:RNA; D063151:Polycomb Repressive Complex 2; D004722:Endoribonucleases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C097081:PPP1R8 protein, human