PROTEIN INTERACTION PARTNERS OF NDRG2

Abstract

NDRG2 is a member of the NDRG gene family, which have diverse roles in nervous system development. Both NDRG2 mRNA and protein are elevated in late-onset Alzheimer's Disease (AD), where the protein is closely associated with senile plaques. In contrast, NDRG4 expression is lowered in AD. Although NDRG proteins contain a structural motif commonly found in hydrolases, there is no evidence that they have catalytic activity and their function is unclear. In order to study NDRG2's cellular function, a yeast 2-hybrid screen was carried out with a mouse brain cDNA library. Specificity of the interaction for NDRG2 vs. other NDRG members was tested. In addition, the region of interaction between NDRG2 and protein interaction partners was determined by deletion and mutation studies. Two protein interaction partners for NDRG2, called PP1 and PP2, were identified. Binding of PP1 to NDRG2 was abolished by mutation of a leucine residue in the hydrolase motif, whereas PP2 required a region C-terminal to the hydrolase motif in NDRG2 for protein interaction. Both PP1 and PP2 did not bind to NDRG4, but PP2 did bind to NDRG1. Finally, the interaction motif for PP1 was shown to reside in the N-terminal portion of the protein. The observed interaction between PP1 and NDRG2 is novel and specific for NDRG2, suggesting a possible role for PP1 in NDRG2's cellular function. PP1 functions as an inhibitor of apoptosis, and further research will be aimed at investigating PP1 expression in AD tissue.