NDRG2 and PRA1 interact and synergistically inhibit T-cell factor/b-catenin signaling

Abstract

NDRG2 is a member of the N-myc downstream regulated gene (NDRG) family, implicated in cell growth and differentiation. Investigation of NDRG2 molecular interactions by yeast two-hybrid screening identified prenylated Rab acceptor-1 (PRA1), involved in vesicle trafficking and protein transport, as binding partner. Binding of NDRG2 (and NDRG1-4) with PRA1 in vitro was confirmed by GST pull-down assay and immunoprecipitation, and colocalization was verified by confocal microscopy in HCT116 cells. Intracellular coexpression showed that NDRG2 and PRA1 synergistically downregulate T-cell factor (TCF) promoter activity and GSK3β phosphorylation. Results suggest that NDRG2 and PRA1 might act synergistically to prevent signaling of TCF/β-catenin. Structured summary of protein interactions: NDRG2a binds to PRA1 by pull down (View interaction) NDRG2a physically interacts with PRA1 by two hybrid (View Interaction: 1, 2) PRA1 physically interacts with NDRG2a by anti tag coimmunoprecipitation (View interaction) NDRG2a, PRA1 and Catenin beta colocalize by cosedimentation (View interaction) NDRG2a and PRA1 colocalize by fluorescence microscopy (View Interaction: 1, 2, 3)