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.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Binding Sites / genetics
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Blotting, Western
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Cell Nucleus / metabolism
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Colorectal Neoplasms / genetics
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / pathology
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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Gene Expression Regulation
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HCT116 Cells
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Humans
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Microscopy, Confocal
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Mutation
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Phosphorylation
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Promoter Regions, Genetic / genetics
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Protein Binding
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Signal Transduction*
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TCF Transcription Factors / genetics*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Two-Hybrid System Techniques
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Vesicular Transport Proteins / genetics
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Vesicular Transport Proteins / metabolism*
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beta Catenin / metabolism*
Substances
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NDRG2 protein, human
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TCF Transcription Factors
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Tumor Suppressor Proteins
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Vesicular Transport Proteins
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beta Catenin
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Green Fluorescent Proteins
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3
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GTP-Binding Proteins
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RABAC1 protein, human