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 ohosphatase-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 NIPP1EED interaction was potentiated by the binding of (d)Grich nucleic acids to the central domain of NIPPI. Nucleic acids also decreased the potency of NIPP1 as an inhibitor of PPi, 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. [ABSTRACT FROM AUTHOR]