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.
Highlights
The nuclear protein NIPP1 interacts with the splicing factors SAP155 and CDC5L and is involved in a late step of spliceosome assembly
Using a yeast two-hybrid screening with NIPP1-(225–351) as bait, we identified EED as a novel interactor of NIPP1 (Fig. 1) and this interaction was subsequently confirmed by co-immunoprecipitation analysis and GST pull-down assays (Figs. 2 and 6)
It is tempting to speculate that the transcriptional repression activity of NIPP1 is mediated by EEDassociated chromatin-modifying enzymes
Summary
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. The FHA domain of NIPP1 interacts with phosphorylated forms of the splicing factors SAP155 [9] and CDC5L [10], which are components of the U2 small nuclear ribonucleoprotein particle and U4/U5/U6 tri-small nuclear ribonucleoprotein particles, respectively. It is not known how residues 225–329 of NIPP1 contribute to spliceosome assembly. The association of HDACs with the PRC2 complex has not been a universal finding [19, 20] Another component of the PRC2 complex is the transcription factor Yin Yang 1 (YY1), which has been suggested to mediate the binding of the PRC2 complex to specific DNA sequences, the so-called Polycomb response elements [26]
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