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.
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.
Mesh Terms:
Animals, COS Cells, Carrier Proteins, Chemical Precipitation, Endoribonucleases, Gene Library, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Mice, Mutagenesis, Site-Directed, Phosphoprotein Phosphatases, Protein Phosphatase 1, RNA, RNA-Binding Proteins, Rabbits, Repressor Proteins, Spliceosomes, Suppression, Genetic, Transcription, Genetic, Two-Hybrid System Techniques, Yeasts
Animals, COS Cells, Carrier Proteins, Chemical Precipitation, Endoribonucleases, Gene Library, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Mice, Mutagenesis, Site-Directed, Phosphoprotein Phosphatases, Protein Phosphatase 1, RNA, RNA-Binding Proteins, Rabbits, Repressor Proteins, Spliceosomes, Suppression, Genetic, Transcription, Genetic, Two-Hybrid System Techniques, Yeasts
J. Biol. Chem.
Date: Aug. 15, 2003
PubMed ID: 12788942
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